Targeting SCF E3 Ligases for Cancer Therapies

Liu, Jing; Peng, Yunhua; Zhang, Jinfang; Long, Jiangang; Liu, Jiankang; Wei, Wenyi

doi:10.1007/978-981-15-1025-0_9

Jing Liu⁷,
Yunhua Peng^7,8,
Jinfang Zhang⁸,
Jiangang Long⁷,
Jiankang Liu⁷ &
…
Wenyi Wei⁸

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1217))

4550 Accesses
26 Citations

Abstract

SKP1-cullin-1-F-box-protein (SCF) E3 ubiquitin ligase complex is responsible for the degradation of proteins in a strictly regulated manner, through which it exerts pivotal roles in regulating various key cellular processes including cell cycle and division, apoptosis, and differentiation. The substrate specificity of the SCF complex largely depends on the distinct F-box proteins, which function in either tumor promotion or suppression or in a context-dependent manner. Among the 69 F-box proteins identified in human genome, FBW7, SKP2, and β-TRCP have been extensively investigated among various types of cancer in respective of their roles in cancer development, progression, and metastasis. Moreover, several specific inhibitors have been developed to target those E3 ligases, and their efficiency in tumors has been determined. In this review, we provide a summary of the roles of SCF E3 ligases in cancer development, as well as the potential application of miRNA or specific inhibitors for cancer therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Chapter: USD 29.95; Price excludes VAT (USA)

eBook: USD 129.00; Price excludes VAT (USA)

Softcover Book: USD 169.99; Price excludes VAT (USA)

Hardcover Book: USD 169.99; Price excludes VAT (USA)

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

5gg:: 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose pentagalloylglucose
AIB1:: Amplified in breast cancer 1
APC:: Adenomatous polyposis coli
APC/C^Cdh1 :: Anaphase-promoting complex/cyclosome Cdh1 complex
ATRA:: All-trans retinoic acid
BLM:: Bloom
C/EBPδ:: CCAAT enhancer binding protein δ
CAND1:: Cullin-associated Nedd8-dissociated protein 1
CDC25A:: Cell division cycle 25 homologue A
CDH1:: E-cadherin
CLL:: Chronic lymphocytic leukemia
CML:: Chronic myeloid leukemia
CPD:: Cdc4 phosphodegron
CRL:: Cullin-RING ubiquitin ligase
CSN:: COP9 signalosome complex
CTD:: Carboxy-terminal domain
D-box:: Destruction box
DD:: Dimerization domain
DEPTOR:: DEP domain-containing mTOR-interacting protein
EBP2:: EBNA1-binding protein 2
EGCG:: Epigallocatechin-3-gallate
ER:: Estrogen receptor
FBW7:: F-box and WD repeat domain-containing 7
FBXO1:: F-box only 1, also known as cyclin F
FDA:: Food and Drug Administration
FOXO1:: Forkhead box O1
FOXP3:: Forkhead box P3
HCC:: Hepatocellular carcinoma
HECT:: Homologous to E6-associated protein C-terminus
HES5:: Hes family bHLH transcription factor 5
HSC:: Hematopoietic stem cells
IκB:: Inhibitor of nuclear factor-κB
KLF5:: Krüppel-like factor 5
LRR:: Leucine-rich repeat
miRNA:: MicroRNA
MMTV:: Mouse mammary tumor virus
NLS:: Nuclear localization signal
NPM:: Nucleophosmin
NSCLC:: Non-small cell lung cancer
ORC1:: Origin recognition complex 1
p21/CIP:: Cyclin-dependent kinase inhibitor 1A, CDKN1A
p27/KIP:: Cyclin-dependent kinase inhibitor 1B, CDKN1B
p57/KIP2:: Cyclin-dependent kinase inhibitor 1C, CDKN1C
PDCD4:: Programmed cell death protein
PGC1α:: Peroxisome proliferator-activated receptor gamma coactivator 1α
PHB2:: Prohibitin 2, also known as REA
PIN 1:: Peptidylprolyl cis/trans isomerases
PS1:: Presenilin 1
PSA:: Prostate-specific antigen
RB1:: Retinoblastoma 1
RBL2:: Retinoblastoma-like protein
RBX1:: RING box 1, also known as regulator of cullins-1 or ROC1
Rictor:: Rapamycin-insensitive companion of mTOR
RING:: Really interesting new gene
SCC:: Squamous cell cancer
SCF:: SKP1-cullin-1-F-box-protein
SKP1:: S-phase kinase-associated protein 1
SKP2:: S-phase kinase-associated protein 2, also known as FBXL1
SLP-1:: Stomatin-like protein 1
SREBP1:: Sterol regulatory element-binding transcription factor 1
T-ALL:: T-cell acute lymphoblastic leukemia
TGIF1:: 5′-TG-3′-interacting factor 1
Tob1:: Transducer of ERBB2
Topo IIα:: DNA topoisomerase 2-alpha
UBA:: E1 ubiquitin-activating enzyme
UBC:: E2 ubiquitin-conjugating enzyme
UPS:: Ubiquitin-proteasome system
VEGFR2:: Vascular endothelial growth factor receptor 2
WHB:: Winged-helix B
YAP1:: Yes-associated protein 1
β-TRCP:: Beta-transducin repeat-containing protein

References

Adamson A, Lin Z, Perez-Ordonez B, Jordan R, Tripp S, Perkins S et al (2001) Expression of Skp2, a p27 ubiquitin ligase in malignant lymphoma: correlation with p27 and proliferation index. Mod Pathol 14(1):154a. https://doi.org/10.1182/blood.V100.8.2950
Article Google Scholar
Akhoondi S, Sun D, von der Lehr N, Apostolidou S, Klotz K, Maljukova A et al (2007) FBXW7/hCDC4 is a general tumor suppressor in human cancer. Cancer Res 67(19):9006–9012. https://doi.org/10.1158/0008-5472.CAN-07-1320
Article CAS PubMed Google Scholar
Akhoondi S, Lindstrom L, Widschwendter M, Corcoran M, Bergh J, Spruck C et al (2010) Inactivation of FBXW7/hCDC4-beta expression by promoter hypermethylation is associated with favorable prognosis in primary breast cancer. Breast Cancer Res 12(6). https://doi.org/10.1186/Bcr2788
Andreu EJ, Lledo E, Poch E, Ivorra C, Albero MP, Martinez-Climent JA et al (2005) BCR-ABL induces the expression of Skp2 through the PI3K pathway to promote p27 (Kip1) degradation and proliferation of chronic myelogenous leukemia cells. Cancer Res 65(8):3264–3272. https://doi.org/10.1158/0008-5472
Article PubMed Google Scholar
Arbini AA, Greco M, Yao JL, Bourne P, Marra E, Hsieh JT et al (2011) Skp2 overexpression is associated with loss of BRCA2 protein in human prostate cancer. Am J Pathol 178(5):2367–2376. https://doi.org/10.1016/j.ajpath.2011.01.050
Article CAS PubMed PubMed Central Google Scholar
Babaei-Jadidi R, Li NN, Saadeddin A, Spencer-Dene B, Jandke A, Muhammad B et al (2011) FBXW7 influences murine intestinal homeostasis and cancer, targeting notch, Jun, and DEK for degradation. J Exp Med 208(2):295–312. https://doi.org/10.1084/jem.20100830
Article CAS PubMed PubMed Central Google Scholar
Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW et al (1996) SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell 86(2):263–274. https://doi.org/10.1016/S0092-8674(00)80098-7
Article CAS PubMed Google Scholar
Balamurugan K, Sharan S, Klarmann KD, Zhang Y, Coppola V, Summers GH et al (2013) FBXW7 alpha attenuates inflammatory signalling by downregulating C/EBP delta and its target gene Tlr4. Nat Commun 4. https://doi.org/10.1038/Ncomms2677
Bedford L, Lowe J, Dick LR, Mayer RJ, Brownell JE (2011) Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets. Nat Rev Drug Discov 10(1):29–46. https://doi.org/10.1038/nrd3321
Article CAS PubMed Google Scholar
Belaidouni N, Peuchmaur M, Perret C, Florentin A, Benarous R, Besnard-Guerin C (2005) Overexpression of human beta TrCP1 deleted of its F box induces tumorigenesis in transgenic mice. Oncogene 24(13):2271–2276. https://doi.org/10.1038/sj.onc.1208418
Article CAS PubMed Google Scholar
Ben-Izhak O, Lahav-Baratz S, Meretyk S, Ben-Eliezer S, Sabo E, Dirnfeld M et al (2003) Inverse relationship between Skp2 ubiquitin ligase and the cyclin dependent kinase inhibitor p27(Kip1) in prostate cancer. J Urol 170(1):241–245. https://doi.org/10.1097/01.ju.0000072113.34524.a7
Article CAS PubMed Google Scholar
Bernassola F, Karin M, Ciechanover A, Melino G (2008) The HECT family of E3 ubiquitin ligases: multiple players in cancer development. Cancer Cell 14(1):10–21. https://doi.org/10.1016/j.ccr.2008.06.001
Article CAS PubMed Google Scholar
Blees JS, Bokesch HR, Rubsamen D, Schulz K, Milke L, Bajer MM et al (2012) Erioflorin stabilizes the tumor suppressor Pdcd4 by inhibiting its interaction with the E3-ligase beta-TrCP1. PLoS One 7(10). https://doi.org/10.1371/journal.pone.0046567
Article CAS PubMed PubMed Central Google Scholar
Bonetti P, Davoli T, Sironi C, Amati B, Pelicci PG, Colombo E (2008) Nucleophosmin and its AML-associated mutant regulate c-Myc turnover through Fbw7 gamma. J Cell Biol 182(1):19–26. https://doi.org/10.1083/jcb.200711040
Article PubMed PubMed Central Google Scholar
Bretones G, Acosta JC, Caraballo JM, Ferrandiz N, Gomez-Casares MT, Albajar M et al (2011) SKP2 oncogene is a direct MYC target gene and MYC down-regulates p27(KIP1) through SKP2 in human leukemia cells. J Biol Chem 286(11):9815–9825. https://doi.org/10.1074/jbc.M110.165977
Article CAS PubMed PubMed Central Google Scholar
Busino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D, Dorrello NV et al (2003) Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature 426(6962):87–91. https://doi.org/10.1038/nature02082
Article CAS PubMed Google Scholar
Caraballo JM, Acosta JC, Cortes MA, Albajar M, Gomez-Casares MT, Batlle-Lopez A et al (2014) High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc and Skp2 expression, confer resistance to apoptosis and antagonize Myc effects on cell cycle. Oncotarget 5(13):4694–4708. https://doi.org/10.18632/oncotarget.2100
Article PubMed PubMed Central Google Scholar
Cardozo T, Pagano M (2004) The SCF ubiquitin ligase: insights into a molecular machine. Nat Rev Mol Cell Biol 5(9):739–751. https://doi.org/10.1038/nrm1471
Article CAS PubMed Google Scholar
Cavadini S, Fischer ES, Bunker RD, Potenza A, Lingaraju GM, Goldie KN et al (2016) Cullin-RING ubiquitin E3 ligase regulation by the COP9 signalosome. Nature 531(7596):598–603. https://doi.org/10.1038/nature17416
Article CAS PubMed Google Scholar
Cavo M (2006) Proteasome inhibitor bortezomib for the treatment of multiple myeloma. Leukemia 20(8):1341–1352. https://doi.org/10.1038/sj.leu.2404278
Article CAS PubMed Google Scholar
Chan CH, Lee SW, Li CF, Wang J, Yang WL, Wu CY et al (2010) Deciphering the transcriptional complex critical for RhoA gene expression and cancer metastasis. Nat Cell Biol 12(5):457–U103. https://doi.org/10.1038/ncb2047
Article CAS PubMed Google Scholar
Chan CH, Li CF, Yang WL, Gao Y, Lee SW, Feng ZZ et al (2012) The Skp2-SCF E3 ligase regulates Akt Ubiquitination, glycolysis, Herceptin sensitivity, and tumorigenesis. Cell 149(5):1098–1111. https://doi.org/10.1016/j.cell.2012.02.065
Article CAS PubMed PubMed Central Google Scholar
Chan CH, Morrow JK, Li CF, Gao Y, Jin GX, Moten A et al (2013) Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression. Cell 154(3):556–568. https://doi.org/10.1016/j.cell.2013.06.048
Article CAS PubMed Google Scholar
Chanan-Khan AA, Lentzsch S, Quach H, Horvath N, Capra M, Ovilla R et al (2016) Daratumumab, bortezomib and dexamethasone versus bortezomib and dexamethasone alone for relapsed or refractory multiple myeloma based on prior treatment exposure: updated efficacy analysis of castor. Blood 128(22):3313
Article Google Scholar
Chander H, Halpern M, Resnick-Silverman L, Manfredi JJ, Germain D (2010) Skp2B attenuates p53 function by inhibiting prohibitin. EMBO Rep 11(3):220–225. https://doi.org/10.1038/embor.2010.2
Article CAS PubMed PubMed Central Google Scholar
Chandra S, Priyadarshini R, Madhavan V, Tikoo S, Hussain M, Mudgal R et al (2013) Enhancement of c-Myc degradation by BLM helicase leads to delayed tumor initiation. J Cell Sci 126(16):3782–3795. https://doi.org/10.1242/jcs.124719
Article CAS PubMed Google Scholar
Chen JY, Wang MC, Hung WC (2009) Transcriptional activation of Skp2 by BCR-ABL in K562 chronic myeloid leukemia cells. Leuk Res 33(11):1520–1524. https://doi.org/10.1016/j.leukres.2009.03.007
Article CAS PubMed Google Scholar
Chen MC, Chen CH, Chuang HC, Kulp SK, Teng CM, Chen CS (2011a) Novel mechanism by which histone deacetylase inhibitors facilitate topoisomerase II alpha degradation in hepatocellular carcinoma cells. Hepatology 53(1):148–159. https://doi.org/10.1002/hep.23964
Article CAS PubMed Google Scholar
Chen MF, Gutierrez GJ, Ronai ZA (2011b) Ubiquitin-recognition protein Ufd1 couples the endoplasmic reticulum (ER) stress response to cell cycle control. Proc Natl Acad Sci U S A 108(22):9119–9124. https://doi.org/10.1073/pnas.1100028108
Article PubMed PubMed Central Google Scholar
Chen Q, Xie WL, Kuhn DJ, Voorhees PM, Lopez-Girona A, Mendy D et al (2008) Targeting the p27 E3 ligase SCFSkp2 results in p27-and Skp2-mediated cell-cycle arrest and activation of autophagy. Blood 111(9):4690–4699. https://doi.org/10.1182/blood-2007-09-112904
Article CAS PubMed PubMed Central Google Scholar
Chuu CP, Kokontis JM, Hiipakka RA, Fukuchi J, Lin HP, Lin CY et al (2011) Androgen suppresses proliferation of castration-resistant LNCaP 104-R2 prostate cancer cells through androgen receptor, Skp2, and c-Myc. Cancer Sci 102(11):2022–2028. https://doi.org/10.1111/j.1349-7006.2011.02043.x
Article CAS PubMed Google Scholar
Cyr DM, Hohfeld J, Patterson C (2002) Protein quality control: U-box-containing E3 ubiquitin ligases join the fold. Trends Biochem Sci 27(7):368–375. https://doi.org/10.1016/S0968-0004(02)02125-4
Article CAS PubMed Google Scholar
Davidovich S, Ben-Izhak O, Shapira M, Futerman B, Hershko DD (2008) Over-expression of Skp2 is associated with resistance to preoperative doxorubicin-based chemotherapy in primary breast cancer. Breast Cancer Res 10(4). https://doi.org/10.1186/Bcr2122
Davis H, Lewis A, Behrens A, Tomlinson I (2014) Investigation of the atypical FBXW7 mutation spectrum in human tumours by conditional expression of a heterozygous propeller tip missense allele in the mouse intestines. Gut 63(5):792–799. https://doi.org/10.1136/gutjnl-2013-304719
Article CAS PubMed Google Scholar
Dehan E, Bassermann F, Guardavaccaro D, Vasiliver-Shamis G, Cohen M, Lowes KN et al (2009) Beta TrCP- and Rsk1/2-mediated degradation of BimEL inhibits apoptosis. Mol Cell 33(1):109–116. https://doi.org/10.1016/j.molcel.2008.12.020
Article CAS PubMed PubMed Central Google Scholar
Deshaies RJ, Joazeiro CAP (2009) RING Domain E3 Ubiquitin Ligases. Annu Rev Biochem 78:399–434. https://doi.org/10.1146/annurev.biochem.78.101807.093809
Article CAS PubMed Google Scholar
Diefenbacher ME, Popov N, Blake SM, Schulein-Volk C, Nye E, Spencer-Dene B et al (2014) The deubiquitinase U5P28 controls intestinal homeostasis and promotes colorectal cancer. J Clin Investig 124(8):3407–3418. https://doi.org/10.1172/JC173733
Article CAS PubMed PubMed Central Google Scholar
Ding QQ, He XG, Hsu JM, Xia WY, Chen CT, Li LY et al (2007) Degradation of Mcl-1 by beta-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Mol Cell Biol 27(11):4006–4017. https://doi.org/10.1128/Mcb.00620-06
Article CAS PubMed Google Scholar
Dong YY, Sui L, Watanabe Y, Sugimoto K, Tokuda M (2003) S-phase kinase-associated protein 2 expression in laryngeal squamous cell carcinomas and its prognostic implications. Oncol Rep 10(2):321–325. https://doi.org/10.3892/or.10.2.321
Article CAS PubMed Google Scholar
Dorrello NV, Peschiaroli A, Guardavaccaro D, Colburn NH, Sherman NE, Pagano M (2006) S6K1- and beta TRCP-mediated degradation of PDCD4 promotes protein translation and cell growth. Science 314(5798):467–471. https://doi.org/10.1126/science.1130276
Article CAS PubMed Google Scholar
Dow R, Hendley J, Pirkmaier A, Musgrove EA, Germain D (2001) Retinoic acid-mediated growth arrest requires ubiquitylation and degradation of the F-box protein Skp2. J Biol Chem 276(49):45945–45951. https://doi.org/10.1074/jbc.M103593200
Article CAS PubMed Google Scholar
Driscoll JJ, Malek E (2015) Pharmacogenomics of Bortezomib in multiple myeloma patients reveals that the ubiquitin ligase SCF-Skp2 promotes drug resistance. Blood 126(23):3021
Article Google Scholar
Duan S, Skaar JR, Kuchay S, Toschi A, Kanarek N, Ben-Neriah Y et al (2011) mTOR generates an auto-amplification loop by triggering the βTrCP-and CK1α-dependent degradation of DEPTOR. Mol Cell 44(2):317–324. https://doi.org/10.1016/j.molcel.2011.09.005
Article CAS PubMed PubMed Central Google Scholar
Duda DM, Borg LA, Scott DC, Hunt HW, Hammel M, Schulman BA (2008) Structural insights into NEDD8 activation of Cullin-RING ligases: conformational control of conjugation. Cell 134(6):995–1006. https://doi.org/10.1016/j.cell.2008.07.022
Article CAS PubMed PubMed Central Google Scholar
Einama T, Kagata Y, Tsuda H, Morita D, Ogata S, Ueda S et al (2006) High-level Skp2 expression in pancreatic ductal adenocarcinoma: correlation with the extent of lymph node metastasis, higher histological grade, and poorer patient outcome. Pancreas 32(4):376–381. https://doi.org/10.1097/01.mpa.0000220862.78248.c4
Article CAS PubMed Google Scholar
Finkin S, Aylon Y, Anzi S, Oren M, Shaulian E (2008) Fbw7 regulates the activity of endoreduplication mediators and the p53 pathway to prevent drug-induced polyploidy. Oncogene 27(32):4411–4421. https://doi.org/10.1038/onc.2008.77
Article CAS PubMed Google Scholar
Fujita T, Liu WJ, Doihara H, Date H, Wan Y (2008) Dissection of the ApC(Cdh1)-Skp2 cascade in breast cancer. Clin Cancer Res 14(7):1966–1975. https://doi.org/10.1158/1078-0432.CCR-07-1585
Article CAS PubMed Google Scholar
Gao D, Inuzuka H, Tan M-KM, Fukushima H, Locasale JW, Liu P et al (2011) mTOR drives its own activation via SCF βTrCP-dependent degradation of the mTOR inhibitor DEPTOR. Mol Cell 44(2):290–303. https://doi.org/10.1016/j.molcel.2011.08.030
Article CAS PubMed PubMed Central Google Scholar
Gao DM, Inuzuka H, Tseng A, Chin RY, Toker A, Wei WY (2009) Phosphorylation by Akt1 promotes cytoplasmic localization of Skp2 and impairs APC-Cdh1-mediated Skp2 destruction. Nat Cell Biol 11(4):397–U392. https://doi.org/10.1038/ncb1847
Article CAS PubMed PubMed Central Google Scholar
Gerstein AV, Almeida TA, Zhao GJ, Chess E, Shih IM, Buhler K et al (2002) APC/CTNNB1 (beta-catenin) pathway alterations in human prostate cancers. Genes Chromosomes Cancer 34(1):9–16. https://doi.org/10.1002/gcc.10037
Article CAS PubMed Google Scholar
Gong JH, Cui Z, Li L, Ma Q, Wang QF, Gao YH et al (2015) MicroRNA-25 promotes gastric cancer proliferation, invasion, and migration by directly targeting F-box and WD-40 domain protein 7, FBXW7. Tumor Biol 36(10):7831–7840. https://doi.org/10.1007/s13277-015-3510-3
Article CAS Google Scholar
Gu ZD, Inomata K, Ishizawa K, Horii A (2007) The FBXW7 beta-form is suppressed in human glioma cells. Biochem Biophys Res Commun 354(4):992–998. https://doi.org/10.1016/j.bbrc.2007.07.080
Article CAS PubMed Google Scholar
Guardavaccaro D, Kudo Y, Boulaire J, Barchi M, Busino L, Donzelli M et al (2003) Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo. Dev Cell 4(6):799–812. https://doi.org/10.1016/S1534-5807(03)00154-0
Article CAS PubMed Google Scholar
Guo Z, Zhou YN, Evers BM, Wang QD (2012) Rictor regulates FBXW7-dependent c-Myc and cyclin E degradation in colorectal cancer cells. Biochem Biophys Res Commun 418(2):426–432. https://doi.org/10.1016/j.bbrc.2012.01.054
Article CAS PubMed PubMed Central Google Scholar
Hagedorn M, Delugin M, Abraldes I, Allain N, Belaud-Rotureau MA, Turmo M et al (2007) FBXW7/hCDC4 controls glioma cell proliferation in vitro and is a prognostic marker for survival in glioblastoma patients. Cell Div 2. https://doi.org/10.1186/1747-1028-2-9
Article PubMed PubMed Central Google Scholar
Handra-Luca A, Ruhin B, Lesty C, Fouret P (2006) P27, SKP2, and extra-cellular signal-related kinase signalling in human salivary gland mucoepidermoid carcinoma. Oral Oncol 42(10):1005–1010. https://doi.org/10.1016/j.oraloncology.2005.12.022
Article CAS PubMed Google Scholar
Hao B, Oehlmann S, Sowa ME, Harper JW, Pavletich NP (2007) Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases. Mol Cell 26(1):131–143. https://doi.org/10.1016/j.molcel.2007.02.022
Article CAS PubMed Google Scholar
Haque R, Song JY, Haque M, Lei FY, Sandhu P, Ni B et al (2017) C-Myc-induced survivin is essential for promoting the notch-dependent T cell differentiation from hematopoietic stem cells. Genes 8(3). https://doi.org/10.3390/Genes8030097
Article PubMed Central Google Scholar
Hart M, Concordet JP, Lassot I, Albert I, del los Santos R, Durand H et al (1999) The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell. Curr Biol 9(4):207–210. https://doi.org/10.1016/S0960-9822(99)80091-8
Article CAS PubMed Google Scholar
Hasler R, Jacobs G, Till A, Grabe N, Cordes C, Nikolaus S et al (2012) Microbial pattern recognition causes distinct functional micro-RNA signatures in primary human monocytes. PLoS One 7(2). https://doi.org/10.1371/journal.pone.0031151
Article PubMed PubMed Central Google Scholar
Herranz D, Ambesi-Impiombato A, Palomero T, Schnell SA, Belver L, Wendorff AA et al (2014) A NOTCH 1-driven MYC enhancer promotes T cell development, transformation and acute lymphoblastic leukemia. Nat Med 20(10):1130–1137. https://doi.org/10.1038/nm.3665
Article CAS PubMed PubMed Central Google Scholar
Hiramatsu Y, Kitagawa K, Suzuki T, Uchida C, Hattori T, Kikuchi H et al (2006) Degradation of Tob1 mediated by SCF (Skp2)-dependent ubiquitination. Cancer Res 66(17):8477–8483. https://doi.org/10.1158/0008-5472.CAN-06-1603
Article CAS PubMed Google Scholar
Hori T, Osaka F, Chiba T, Miyamoto C, Okabayashi K, Shimbara N et al (1999) Covalent modification of all members of human cullin family proteins by NEDD8. Oncogene 18(48):6829–6834. https://doi.org/10.1038/sj.onc.1203093
Article CAS PubMed Google Scholar
Hsu JD, Kao SH, Ou TT, Chen YJ, Li YJ, Wang CJ (2011) Gallic acid induces G2/M phase arrest of breast cancer cell MCF-7 through stabilization of p27(Kip1) attributed to disruption of p27(Kip1)/Skp2 complex. J Agric Food Chem 59(5):1996–2003. https://doi.org/10.1021/jf103656v
Article CAS PubMed Google Scholar
Hua JS, Ding TL, Yang LJ (2016) Dysfunction of microRNA-32 regulates ubiquitin ligase FBXW7 in multiple myeloma disease. Onco Targets Ther 9:6573–6579. https://doi.org/10.2147/Ott.S105945
Article CAS PubMed PubMed Central Google Scholar
Huang H, Regan KM, Wang F, Wang DP, Smith DI, van Deursen JMA et al (2005) Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation. Proc Natl Acad Sci USA 102(5):1649–1654. https://doi.org/10.1073/pnas.0406789102
Article CAS PubMed PubMed Central Google Scholar
Huang HC, Way TD, Lin CL, Lin JK (2008) EGCG stabilizes p27(kip1) in E2-stimulated MCF-7 cells through down-regulation of the Skp2 protein. Endocrinology 149(12):5972–5983. https://doi.org/10.1210/en.2008-0408
Article CAS PubMed Google Scholar
Imura S, Tovuu LO, Utsunomiya T, Morine Y, Ikemoto T, Arakawa Y et al (2014) The role of Fbxw7 expression in hepatocellular carcinoma and adjacent non-tumor liver tissue. J Gastroenterol Hepatol 29(10):1822–1829. https://doi.org/10.1111/jgh.12623
Article CAS PubMed Google Scholar
Inuzuka H, Shaik S, Onoyama I, Gao DM, Tseng A, Maser RS et al (2011) SCFFBW7 regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature 471(7336):104–U128. https://doi.org/10.1038/nature09732
Article CAS PubMed PubMed Central Google Scholar
Inuzuka H, Gao D, Finley LW, Yang W, Wan L, Fukushima H et al (2012) Acetylation-dependent regulation of Skp2 function. Cell 150(1):179–193. https://doi.org/10.1016/j.cell.2012.05.038
Article CAS PubMed PubMed Central Google Scholar
Iskandarani A, Bhat AA, Siveen KS, Prabhu KS, Kuttikrishnan S, Khan MA et al (2016) Bortezomib-mediated downregulation of S-phase kinase protein-2 (SKP2) causes apoptotic cell death in chronic myelogenous leukemia cells. J Transl Med 14. https://doi.org/10.1186/s12967-016-0823-y
Jiang JT, Pan YQ, Regan KM, Wu CP, Zhang XG, Tindall DJ et al (2012b) Androgens repress expression of the f-box protein Skp2 via p107 dependent and independent mechanisms in LNCaP prostate cancer cells. Prostate 72(2):225–232. https://doi.org/10.1002/pros.21430
Article CAS PubMed Google Scholar
Jiang XL, Xing HY, Kim TM, Jung YC, Huang W, Yang HW et al (2012a) Numb regulates glioma stem cell fate and growth by altering epidermal growth factor receptor and Skp1-Cullin-F-box ubiquitin ligase activity. Stem Cells 30(7):1313–1326. https://doi.org/10.1002/stem.1120
Article CAS PubMed PubMed Central Google Scholar
Jiang XS, Li XF, Wu FF, Gao HL, Wang GR, Zheng H et al (2017) Overexpression of miR-92a promotes the tumor growth of osteosarcoma by suppressing F-box and WD repeat-containing protein 7. Gene 606:10–16. https://doi.org/10.1016/j.gene.2017.01.002
Article CAS PubMed Google Scholar
Jin JP, Shirogane T, Xu L, Nalepa G, Qin J, Elledge SJ et al (2003) SCF beta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. Genes Dev 17(24):3062–3074. https://doi.org/10.1101/gad.1157503
Article CAS PubMed PubMed Central Google Scholar
Kamura T, Hara T, Kotoshiba S, Yada M, Ishida N, Imaki H et al (2003) Degradation of p57(Kip2) mediated by SCFSkp2 - dependent ubiquitylation. Proc Natl Acad Sci USA 100(18):10231–10236. https://doi.org/10.1073/pnas.1831009100
Article CAS PubMed PubMed Central Google Scholar
Kim CJ, Song JH, Cho YG, Kim YS, Kim SY, Nam SW et al (2007) Somatic mutations of the beta-TrCP gene in gastric cancer. APMIS 115(2):127–133. https://doi.org/10.1111/j.1600-0463.2007.apm_562.x
Article CAS PubMed Google Scholar
Kim SY, Herbst A, Tworkowski KA, Salghetti SE, Tansey WP (2003) Skp2 regulates Myc protein stability and activity. Mol Cell 11(5):1177–1188. https://doi.org/10.1016/S1097-2765(03)00173-4
Article CAS PubMed Google Scholar
Kimura T, Gotoh M, Nakamura Y, Arakawa H (2003) hCDC4b, a regulator of cyclin E, as a direct transcriptional target of p53. Cancer Sci 94(5):431–436. https://doi.org/10.1111/j.1349-7006.2003.tb01460.x
Article CAS PubMed Google Scholar
King B, Trimarchi T, Reavie L, Xu LY, Mullenders J, Ntziachristos P et al (2013) The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability. Cell 153(7):1552–1566. https://doi.org/10.1016/j.cell.2013.05.041
Article CAS PubMed PubMed Central Google Scholar
Kitagawa M, Lee SH, McCormick F (2008) Skp2 suppresses p53-dependent apoptosis by inhibiting p300. Mol Cell 29(2):217–231. https://doi.org/10.1016/j.molcel.2007.11.036
Article CAS PubMed Google Scholar
Klinakis A, Szaboics M, Politi K, Kiaris H, Artavanis-Tsakonas S, Efstratiadis A (2006) Myc is a Notch1 transcriptional target and a requisite for Notch1-induced mammary tumorigenesis in mice. Proc Natl Acad Sci U S A 103(24):9262–9267. https://doi.org/10.1073/pnas.0603371103
Article CAS PubMed PubMed Central Google Scholar
Koepp DM, Schaefer LK, Ye X, Keyomarsi K, Chu C, Harper JW et al (2001) Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science 294(5540):173–177. https://doi.org/10.1126/science.1065203
Article CAS PubMed Google Scholar
Koh MS, Ittmann M, Kadmon D, Thompson TC, Leach FS (2006) CDC4 gene expression as potential biomarker for targeted therapy in prostate cancer. Cancer Biol Ther 5(1):78–83. https://doi.org/10.4161/cbt.5.1.2290
Article CAS PubMed Google Scholar
Kossatz U, Dietrich N, Zender L, Buer J, Manns MP, Malek NP (2004) Skp2-dependent degradation of p27kip1 is essential for cell cycle progression. Genes Dev 18(21):2602–2607. https://doi.org/10.1101/gad.321004
Article CAS PubMed PubMed Central Google Scholar
Kudo Y, Kitajima S, Sato S, Miyauchi M, Ogawa I, Takata T (2001) High expression of S-phase kinase-interacting protein 2, human F-box protein, correlates with poor prognosis in oral squamous cell carcinomas. Cancer Res 61(19):7044–7047
CAS PubMed Google Scholar
Kudo Y, Guardavaccaro D, Santamaria PG, Koyama-Nasu R, Latres E, Bronson R et al (2004) Role of F-box protein beta Trcp1 in mammary gland development and tumorigenesis. Mol Cell Biol 24(18):8184–8194. https://doi.org/10.1128/Mcb.24.18.8184-8194.2004
Article CAS PubMed PubMed Central Google Scholar
Kurashige J, Watanabe M, Iwatsuki M, Kinoshita K, Saito S, Hiyoshi Y et al (2012) Overexpression of microRNA-223 regulates the ubiquitin ligase FBXW7 in oesophageal squamous cell carcinoma. Br J Cancer 106(1):182–188. https://doi.org/10.1038/bjc.2011.509
Article CAS PubMed Google Scholar
Latres E, Chiarle R, Schulman BA, Pavletich NP, Pellicer A, Inghirami C et al (2001) Role of the F-box protein Skp2 in lymphomagenesis. Proc Natl Acad Sci USA 98(5):2515–2520. https://doi.org/10.1073/pnas.041475098
Article CAS PubMed PubMed Central Google Scholar
Lerner M, Lundgren J, Akhoondi S, Jahn A, Ng HF, Moqadam FA et al (2011) MiRNA-27a controls FBW7/hCDC4-dependent cyclin E degradation and cell cycle progression. Cell Cycle 10(13):2172–2183. https://doi.org/10.4161/cc.10.13.16248
Article CAS PubMed Google Scholar
Li JH, Pauley AM, Myers RL, Shuang RQ, Brashler JR, Yan RQ et al (2002) SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production. J Neurochem 82(6):1540–1548. https://doi.org/10.1046/j.1471-4159.2002.01105.x
Article CAS PubMed Google Scholar
Lin HK, Wang GC, Chen ZB, Teruya-Feldstein J, Liu Y, Chan CH et al (2009) Phosphorylation-dependent regulation of cytosolic localization and oncogenic function of Skp2 by Akt/PKB. Nat Cell Biol 11(4):420–U144. https://doi.org/10.1038/ncb1849.
Article CAS PubMed PubMed Central Google Scholar
Lin HK, Chen ZB, Wang GC, Nardella C, Lee SW, Chan CH et al (2010) Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature 464(7287):374–U366. https://doi.org/10.1038/nature08815
Article CAS PubMed PubMed Central Google Scholar
Liu JD, Furukawa M, Matsumoto T, Xiong Y (2002) NEDD8 modification of CUL1 short article dissociates p120(CAND1), an inhibitor of CULl-SKP1 binding and SCIF ligases. Mol Cell 10(6):1511–1518. https://doi.org/10.1016/S1097-2765(02)00783-9
Article CAS PubMed Google Scholar
Liu YH, Tong ZW, Li T, Chen Q, Zhuo LT, Li WG et al (2012) Hepatitis B virus X protein stabilizes amplified in breast cancer 1 protein and cooperates with it to promote human hepatocellular carcinoma cell invasiveness. Hepatology 56(3):1015–1024. https://doi.org/10.1002/hep.25751
Article CAS PubMed Google Scholar
Lu D, Davis MPA, Abreu-Goodger C, Wang W, Campos LS, Siede J et al (2012) MiR-25 regulates Wwp2 and Fbxw7 and promotes reprogramming of mouse fibroblast cells to iPSCs. PLoS One 7(8). https://doi.org/10.1371/journal.pone.0040938
Article CAS PubMed PubMed Central Google Scholar
Lu LF, Schulz H, Wolf DA (2002) The F-box protein SKP2 mediates androgen control of p27 stability in LNCaP human prostate cancer cells. BMC Cell Biol 3. https://doi.org/10.1186/1471-2121-3-22
Article CAS PubMed PubMed Central Google Scholar
Lu MD, Ma JB, Xue WQ, Cheng C, Wang Y, Zhao YM et al (2009) The expression and prognosis of FOXO3a and Skp2 in human hepatocellular carcinoma. Pathol Oncol Res 15(4):679–687. https://doi.org/10.1007/s12253-009-9171-z
Article CAS PubMed Google Scholar
Lu YH, Zi XL, Pollak M (2004) Molecular mechanisms underlying IGF-I-induced attenuation of the growth-inhibitory activity of trastuzumab (Herceptin) on SKBR3 breast cancer cells. Int J Cancer 108(3):334–341. https://doi.org/10.1002/ijc.11445
Article CAS PubMed Google Scholar
Ma J, Cheng L, Liu H, Zhang J, Shi Y, Zeng FP et al (2013) Genistein down-regulates miR-223 expression in pancreatic cancer cells. Curr Drug Targets 14(10):1150–1156. https://doi.org/10.2174/13894501113149990187
Article CAS PubMed Google Scholar
Malek E, Abdel-Malek MAY, Jagannathan S, Vad N, Karns R, Jegga AG et al (2017) Pharmacogenomics and chemical library screens reveal a novel SCFSKP2 inhibitor that overcomes Bortezomib resistance in multiple myeloma. Leukemia 31(3):645–653. https://doi.org/10.1038/leu.2016.258
Article CAS PubMed Google Scholar
Mao JH, Perez-Iosada J, Wu D, DelRosario R, Tsunematsu R, Nakayama KI et al (2004) Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene. Nature 432(7018):775–779. https://doi.org/10.1038/nature03155
Article CAS PubMed Google Scholar
Mao JH, Kim IJ, Wu D, Climent J, Kang HC, DelRosario R et al (2008) FBXW7 targets mTOR for degradation and cooperates with PTEN in tumor suppression. Science 321(5895):1499–1502. https://doi.org/10.1126/science.1162981
Article CAS PubMed PubMed Central Google Scholar
Margottin F, Bour SP, Durand H, Selig L, Benichou S, Richard V et al (1998) A novel human WD protein, h-beta TrCP, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif. Mol Cell 1(4):565–574. https://doi.org/10.1016/S1097-2765(00)80056-8
Article CAS PubMed Google Scholar
Margottin-Goguet F, Hsu JY, Loktev A, Hsieh HM, Reimann JDR, Jackson PK (2003) Prophase destruction of Emi1 by the SCF beta TrCP/Slimb ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Dev Cell 4(6):813–826. https://doi.org/10.1016/S1534-5807(03)00153-9
Article CAS PubMed Google Scholar
Marti A, Wirbelauer C, Scheffner M, Krek W (1999) Interaction between ubiquitin-protein ligase SCFSKP2 and E2F-1 underlies the regulation of E2F-1 degradation. Nat Cell Biol 1(1):14–19. https://doi.org/10.1038/8984
Article CAS PubMed Google Scholar
Maser RS, Choudhury B, Campbell PJ, Feng B, Wong KK, Protopopov A et al (2007) Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers. Nature 447(7147):966–U963. https://doi.org/10.1038/nature05886
Article CAS PubMed PubMed Central Google Scholar
Masuda T, Inoue H, Sonoda H, Mine S, Yoshikawa Y, Nakayama K et al (2002) Clinical and biological significance of S-phase kinase-associated protein 2 (Skp2) gene expression in gastric carcinoma: modulation of malignant phenotype by Skp2 overexpression, possibly via p27 proteolysis. Cancer Res 62(13):3819–3825
CAS PubMed Google Scholar
Matsumoto A, Onoyama I, Nakayama KI (2006) Expression of mouse Fbxw7 isoforms is regulated in a cell cycle- or p53-dependent manner. Biochem Biophys Res Commun 350(1):114–119. https://doi.org/10.1016/j.bbrc.2006.09.003
Article CAS PubMed Google Scholar
Matsumoto A, Tateishi Y, Onoyama I, Okita Y, Nakayama K, Nakayama KI (2011) Fbxw7 beta resides in the endoplasmic reticulum membrane and protects cells from oxidative stress. Cancer Sci 102(4):749–755. https://doi.org/10.1111/j.1349-7006.2011.01851.x
Article CAS PubMed Google Scholar
Matsuoka S, Oike Y, Onoyama I, Iwama A, Arai F, Takubo K et al (2008) Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL. Genes Dev 22(8):986–991. https://doi.org/10.1101/gad.1621808
Article CAS PubMed PubMed Central Google Scholar
Mendez J, Zou-Yang XH, Kim SY, Hidaka M, Tansey WP, Stillman B (2002) Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication. Mol Cell 9(3):481–491. https://doi.org/10.1016/S1097-2765(02)00467-7
Article CAS PubMed Google Scholar
Min SH, Lau AW, Lee TH, Inuzuka H, Wei S, Huang PY et al (2012) Negative regulation of the stability and tumor suppressor function of Fbw7 by the Pin1 prolyl isomerase. Mol Cell 46(6):771–783. https://doi.org/10.1016/j.molcel.2012.04.012
Article CAS PubMed PubMed Central Google Scholar
Min YH, Cheong JW, Lee MH, Kim JY, Lee ST, Hahn JS et al (2004) Elevated S-phase kinase-associated protein 2 protein expression in acute myelogenous leukemia: its association with constitutive phosphorylation of phosphatase and tensin homologue protein and poor prognosis. Clin Cancer Res 10(15):5123–5130. https://doi.org/10.1158/1078-0432.Ccr-04-0136
Article CAS PubMed Google Scholar
Moberg KH, Bell DW, Wahrer DCR, Haber DA, Hariharan IK (2001) Archipelago regulates Cyclin E levels in drosophila and is mutated in human cancer cell lines. Nature 413(6853):311–316. https://doi.org/10.1038/35095068
Article CAS PubMed Google Scholar
Morimoto M, Nishida T, Nagayama Y, Yasuda H (2003) Nedd8-modification of Cul1 is promoted by Roc1 as a Nedd8-E3 ligase and regulates its stability. Biochem Biophys Res Commun 301(2):392–398. https://doi.org/10.1016/S0006-291x(02)03051-6
Article CAS PubMed Google Scholar
Moro L, Arbini AA, Marra E, Greco M (2006) Up-regulation of Skp2 after prostate cancer cell adhesion to basement membranes results in BRCA2 degradation and cell proliferation. J Biol Chem 281(31):22100–22107. https://doi.org/10.1074/jbc.M604636200
Article CAS PubMed Google Scholar
Muerkoster S, Arlt A, Sipos B, Witt M, Grossmann M, Kloppel G et al (2005) Increased expression of the E3-ubiquitin ligase receptor subunit beta TRCP1 relates to constitutive nuclear factor-kappa B activation and chemoresistance in pancreatic carcinoma cells. Cancer Res 65(4):1316–1324. https://doi.org/10.1158/0008-5472.Can-04-1626
Article PubMed Google Scholar
Muzny DM, Bainbridge MN, Chang K, Dinh HH, Drummond JA, Fowler G et al (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487(7407):330–337. https://doi.org/10.1038/nature11252
Article CAS Google Scholar
Nakayama K, Nagahama H, Minamishima YA, Matsumoto M, Nakamichi I, Kitagawa K et al (2000) Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication. EMBO J 19(9):2069–2081. https://doi.org/10.1093/emboj/19.9.2069
Article CAS PubMed PubMed Central Google Scholar
Nakayama K, Hatakeyama S, Maruyama S, Kikuchi A, Onoe K, Good RA et al (2003) Impaired degradation of inhibitory subunit of NF-kappa B (I kappa B) and beta-catenin as a result of targeted disruption of the beta-TrCP1 gene. Proc Natl Acad Sci USA 100(15):8752–8757. https://doi.org/10.1073/pnas.1133216100
Article CAS PubMed PubMed Central Google Scholar
Nash P, Tang XJ, Orlicky S, Chen QH, Gertler FB, Mendenhall MD et al (2001) Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication. Nature 414(6863):514–521. https://doi.org/10.1038/35107009
Article CAS PubMed Google Scholar
Nateri AS, Riera-Sans L, Da Costa C, Behrens A (2004) The ubiquitin ligase SCFFbw7 antagonizes apoptotic JNK signaling. Science 303(5662):1374–1378. https://doi.org/10.1126/science.1092880
Article CAS PubMed Google Scholar
Nguyen PL, Lin DI, Lei JY, Fiorentino M, Mueller E, Weinstein MH et al (2011) The impact of Skp2 overexpression on recurrence-free survival following radical prostatectomy. Urol Oncol 29(3):302–308. https://doi.org/10.1016/j.urolonc.2009.03.022
Article CAS PubMed Google Scholar
Nie L, Wu H, Sun XH (2008) Ubiquitination and degradation of Tal1/SCL are induced by notch signaling and depend on Skp2 and CHIP. J Biol Chem 283(2):684–692. https://doi.org/10.1074/jbc.M704981200
Article CAS PubMed Google Scholar
Nishitani H, Sugimoto N, Roukos V, Nakanishi Y, Saijo M, Obuse C et al (2006) Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. EMBO J 25(5):1126–1136. https://doi.org/10.1038/sj,emboj.7601002
Article CAS PubMed PubMed Central Google Scholar
Olson BL, Hock MB, Ekholm-Reed S, Wohlschlegel JA, Dev KK, Kralli A et al (2008) SCFCdc4 acts antagonistically to the PGC-1 alpha transcriptional coactivator by targeting it for ubiquitin-mediated proteolysis. Genes Dev 22(2):252–264. https://doi.org/10.1101/gad.1624208
Article CAS PubMed PubMed Central Google Scholar
Onoyama I, Tsunematsu R, Matsumoto A, Kimura T, de Alboran IM, Nakayama K et al (2007) Conditional inactivation of Fbxw7 impairs cell-cycle exit during T cell differentiation and results in lymphomatogenesis. J Exp Med 204(12):2875–2888. https://doi.org/10.1084/Jem.20062299
Article CAS PubMed PubMed Central Google Scholar
Onoyama I, Suzuki A, Matsumoto A, Tomita K, Katagiri H, Oike Y et al (2011) Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver. J Clin Investig 121(1):342–354. https://doi.org/10.1172/JCI40725
Article CAS PubMed Google Scholar
Orlicky S, Tang XJ, Willems A, Tyers M, Sicheri F (2003) Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase. Cell 112(2):243–256. https://doi.org/10.1016/S0092-8674(03)00034-5
Article CAS PubMed Google Scholar
Pernicova Z, Slabakova E, Kharaishvili G, Bouchal J, Kral M, Kunicka Z et al (2011) Androgen depletion induces senescence in prostate cancer cells through down-regulation of Skp2. Neoplasia 13(6):526–536. https://doi.org/10.1593/neo.11182
Article CAS PubMed PubMed Central Google Scholar
Popov N, Schulein C, Jaenicke LA, Eilers M (2010) Ubiquitylation of the amino terminus of Myc by SCF beta-TrCP antagonizes SCFFbw7-mediated turnover. Nat Cell Biol 12(10):973–981. https://doi.org/10.1038/ncb2104
Article CAS PubMed Google Scholar
Qu X, Shen LL, Zheng Y, Cui Y, Feng ZH, Liu F et al (2014) A signal transduction pathway from TGF-beta 1 to SKP2 via Akt1 and c-Myc and its correlation with progression in human melanoma. J Investig Dermatol 134(1):159–167. https://doi.org/10.1038/jid.2013.281
Article CAS PubMed Google Scholar
Radke S, Pirkmaier A, Germain D (2005) Differential expression of the F-box proteins Skp2 and Skp2B in breast cancer. Oncogene 24(21):3448–3458. https://doi.org/10.1038/sj.onc.1208328
Article CAS PubMed Google Scholar
Rajagopalan H, Jallepalli PV, Rago C, Velculescu VE, Kinzler KW, Vogelstein B et al (2004) Inactivation of hCDC4 can cause chromosomal instability. Nature 428(6978):77–81. https://doi.org/10.1038/nature02313
Article CAS PubMed Google Scholar
Ray D, Osmundson EC, Kiyokawa H (2006) Constitutive and UV-induced fibronectin degradation is a ubiquitination-dependent process controlled by beta-TrCP. J Biol Chem 281(32):23060–23065. https://doi.org/10.1074/jbc.M604311200
Article CAS PubMed Google Scholar
Rebello RJ, Pearson RB, Hannan RD, Furic L (2017) Therapeutic approaches targeting MYC-driven prostate cancer. Genes 8(2). https://doi.org/10.3390/Genes8020071
Article PubMed Central Google Scholar
Richardson PG, Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D et al (2003) A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 348(26):2609–2617. https://doi.org/10.1056/Nejmoa030288
Article CAS PubMed Google Scholar
Rico-Bautista E, Yang CC, Lu LF, Roth GP, Wolf DA (2010) Chemical genetics approach to restoring p27Kip1 reveals novel compounds with antiproliferative activity in prostate cancer cells. BMC Biol 8. https://doi.org/10.1186/1741-7007-8-153
Roy S, Kaur M, Agarwal C, Tecklenburg M, Sclafani RA, Agarwal R (2007) P21 and p27 induction by silibinin is essential for its cell cycle arrest effect in prostate carcinoma cells. Mol Cancer Ther 6(10):2696–2707. https://doi.org/10.1158/1535-7163.MCT-07-0104
Article CAS PubMed Google Scholar
Saitoh T, Katoh M (2001) Expression profiles of beta TRCP1 and beta TRCP2, and mutation analysis of beta TRCP2 in gastric cancer. Int J Oncol 18(5):959–964
CAS PubMed Google Scholar
Sancho R, Jandke A, Davis H, Diefenbacher ME, Tomlinson I, Behrens A (2010) F-box and WD repeat domain-containing 7 regulates intestinal cell lineage commitment and is a haploinsufficient tumor suppressor. Gastroenterology 139(3):929–941. https://doi.org/10.1053/j.gastro.2010.05.078
Article CAS PubMed Google Scholar
Sancho R, Blake SM, Tendeng C, Clurman BE, Lewis J, Behrens A (2013) Fbw7 repression by Hes5 creates a feedback loop that modulates notch-mediated intestinal and neural stem cell fate decisions. PLoS Biol 11(6). https://doi.org/10.1371/journal.pbio.1001586
Article CAS PubMed PubMed Central Google Scholar
Sasajima H, Nakagawa K, Kashiwayanagi M, Yokosawa H (2012) Polyubiquitination of the B-cell translocation gene 1 and 2 proteins is promoted by the SCF ubiquitin ligase complex containing beta TrCP. Biol Pharm Bull 35(9):1539–1545. https://doi.org/10.1248/bpb.b12-00330
Article CAS PubMed Google Scholar
Seki R, Ohshima K, Fujisaki T, Uike N, Kawano F, Gondo H et al (2010) Prognostic significance of S-phase kinase-associated protein 2 and p27(kip1) in patients with diffuse large B-cell lymphoma: effects of rituximab. Ann Oncol 21(4):833–841. https://doi.org/10.1093/annonc/mdp481
Article CAS PubMed Google Scholar
Shapira M, Kakiashvili E, Rosenberg T, Hershko DD (2006) The mTOR inhibitor rapamycin down-regulates the expression of the ubiquitin ligase subunit Skp2 in breast cancer cells. Breast Cancer Res 8(4):R46. https://doi.org/10.1186/Bcr1533
Article PubMed PubMed Central Google Scholar
Shaughnessy J (2005) Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27(Kip1) and an aggressive clinical course in multiple myeloma. Hematology 10:117–126. https://doi.org/10.1080/10245330512331390140
Article CAS PubMed Google Scholar
Shim EH, Johnson L, Noh HL, Kim YJ, Sun H, Zeiss C et al (2003) Expression of the F-box protein SKP2 induces hyperplasia, dysplasia, and low-grade carcinoma in the mouse prostate. Cancer Res 63(7):1583–1588
CAS PubMed Google Scholar
Shouksmith AE, Evans LE, Tweddle DA, Miller DC, Willmore E, Newell DR et al (2015) Synthesis and activity of putative small-molecule inhibitors of the F-box protein SKP2. Aust J Chem 68(4):660–679. https://doi.org/10.1071/CH14586
Article CAS Google Scholar
Sistrunk C, Kim SH, Wang X, Lee SH, Kim Y, Macias E et al (2013) Skp2 deficiency inhibits chemical skin tumorigenesis independent of p27(Kip1) accumulation. Am J Pathol 182(5):1854–1864. https://doi.org/10.1016/j.ajpath.2013.01.016
Article CAS PubMed PubMed Central Google Scholar
Sonoda H, Inoue H, Ogawa K, Utsunomiya T, Masuda TA, Mori M (2006) Significance of Skp2 expression in primary breast cancer. Clin Cancer Res 12(4):1215–1220. https://doi.org/10.1158/1078-0432.CCR-05-1709
Article CAS PubMed Google Scholar
Spiegelman VS, Slaga TJ, Pagano M, Minamoto T, Ronai Z, Fuchs SY (2000) Wnt/beta-catenin signaling induces the expression and activity of beta TrCP ubiquitin ligase receptor. Mol Cell 5(5):877–882. https://doi.org/10.1016/S1097-2765(00)80327-5
Article CAS PubMed Google Scholar
Spruck C (2011) miR-27a regulation of SCFFbw7 in cell division control and cancer. Cell Cycle 10(19):3232–3232. https://doi.org/10.4161/cc.10.19.17125
Article CAS PubMed Google Scholar
Strack P, Caligiuri M, Pelletier M, Boisclair M, Theodoras A, Beer-Romero P et al (2000) SCF beta-TRCP and phosphorylation dependent ubiquitination of I kappa B alpha catalyzed by Ubc3 and Ubc4. Oncogene 19(31):3529–3536. https://doi.org/10.1038/sj.onc.1203647
Article CAS PubMed Google Scholar
Strohmaier H, Spruck CH, Kaiser P, Won KA, Sangfelt O, Reed SI (2001) Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature 413(6853):316–322. https://doi.org/10.1038/35095076
Article CAS PubMed Google Scholar
Sun LC, Cai L, Yu Y, Meng QW, Cheng XS, Zhao YB et al (2007) Knockdown of s-phase kinase-associated protein-2 expression in MCF-7 inhibits cell growth and enhances the cytotoxic effects of epirubicin. Acta Biochim Biophys Sin 39(12):999–1007. https://doi.org/10.1111/j.1745-7270.2007.00361.x
Article CAS PubMed Google Scholar
Sun XF, Sun JP, Hou HT, Li K, Liu X, Ge QX (2016) MicroRNA-27b exerts an oncogenic function by targeting Fbxw7 in human hepatocellular carcinoma. Tumor Biol 37(11):15325–15332. https://doi.org/10.1007/s13277-016-5444-9
Article CAS Google Scholar
Sundqvist A, Bengoechea-Alonso MT, Ye X, Lukiyanchuk V, Jin JP, Harper JW et al (2005) Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCFFbw7. Cell Metab 1(6):379–391. https://doi.org/10.1016/j.cmet.2005.04.010
Article CAS PubMed Google Scholar
Suzuki H, Chiba T, Suzuki T, Fujita T, Ikenoue T, Omata M et al (2000) Homodimer of two F-box proteins beta TrCP1 or beta TrCP2 binds to I kappa B alpha for signal-dependent ubiquitination. J Biol Chem 275(4):2877–2884. https://doi.org/10.1074/jbc.275.4.2877
Article CAS PubMed Google Scholar
Tan MJ, Gallegos JR, Gu QY, Huang YH, Li J, Jin YT et al (2006) SAG/ROC-SCF beta-TrCP E3 ubiquitin ligase promotes pro-caspase-3 degradation as a mechanism of apoptosis protection. Neoplasia 8(12):1042–1054. https://doi.org/10.1593/neo.06568
Article CAS PubMed PubMed Central Google Scholar
Tang B, Lei BA, Qi GY, Liang XS, Tang F, Yuan SG et al (2016) MicroRNA-155-3p promotes hepatocellular carcinoma formation by suppressing FBXW7 expression. J Exp Clin Cancer Res 35. https://doi.org/10.1186/s13046-016-0371-6
Tedesco D, Lukas J, Reed SI (2002) The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein-ubiquitin ligase SCFSkp2. Genes Dev 16(22):2946–2957. https://doi.org/10.1101/gad.1011202
Article CAS PubMed PubMed Central Google Scholar
Teng CL, Hsieh YC, Phan L, Shin J, Gully C, Velazquez-Torres G et al (2012) FBXW7 is involved in Aurora B degradation. Cell Cycle 11(21):4059–4068. https://doi.org/10.4161/cc.22381
Article CAS PubMed PubMed Central Google Scholar
Tetzlaff MT, Yu W, Li MM, Zhang PM, Finegold M, Mahon K et al (2004) Defective cardiovascular development and elevated cyclin E and notch proteins in mice lacking the Fbw7 F-box protein. Proc Natl Acad Sci USA 101(10):3338–3345. https://doi.org/10.1073/pnas.0307875101
Article CAS PubMed PubMed Central Google Scholar
Thompson BJ, Jankovic V, Gao J, Buonamici S, Vest A, Lee JM et al (2008) Control of hematopoietic stem cell quiescence by the E3 ubiquitin ligase Fbw7. J Exp Med 205(6):1395–1408. https://doi.org/10.1084/jem.20080277
Article CAS PubMed PubMed Central Google Scholar
Tosco P, Maggiore GML, Forni P, Berrone S, Chiusa L, Garzino-Demo P (2011) Correlation between Skp2 expression and nodal metastasis in stage I and II oral squamous cell carcinomas. Oral Dis 17(1):102–108. https://doi.org/10.1111/j.1601-0825.2010.01713.x
Article CAS PubMed Google Scholar
Tsunematsu R, Nakayama K, Oike Y, Nishiyama M, Ishida N, Hatakeyama S et al (2004) Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development. J Biol Chem 279(10):9417–9423. https://doi.org/10.1074/jbc.M312337200
Article CAS PubMed Google Scholar
Tsvetkov LM, Yeh KH, Lee SJ, Sun H, Zhang H (1999) P27(Kip1) ubiquitination and degradation is regulated by the SCFSkp2 complex through phosphorylated Thr187 in p27. Curr Biol 9(12):661–664. https://doi.org/10.1016/S0960-9822(99)80290-5
Article CAS PubMed Google Scholar
Tu KS, Zheng X, Zan XF, Han SS, Yao YM, Liu QG (2012) Evaluation of Fbxw7 expression and its correlation with the expression of c-Myc, cyclin E and p53 in human hepatocellular carcinoma. Hepatol Res 42(9):904–910. https://doi.org/10.1111/j.1872-034X.2012.01005.x
Article CAS PubMed Google Scholar
Tu KS, Yang W, Li C, Zheng X, Lu ZT, Guo C et al (2014) Fbxw7 is an independent prognostic marker and induces apoptosis and growth arrest by regulating YAP abundance in hepatocellular carcinoma. Mol Cancer 13. https://doi.org/10.1186/1476-4598-13-110
Article PubMed PubMed Central Google Scholar
Uddin S, Hussain A, Ahmed M, Belgaumi A, Al-Dayel F, Ajarim D et al (2008) S-phase kinase protein 2 is an attractive therapeutic target in a subset of diffuse large B-cell lymphoma. J Pathol 216(4):483–494. https://doi.org/10.1002/path.2433
Article CAS PubMed Google Scholar
Umanskaya K, Radke S, Chander H, Monardo R, Xu X, Pan ZQ et al (2007) Skp2B stimulates mammary gland development by inhibiting REA, the repressor of the estrogen receptor. Mol Cell Biol 27(21):7615–7622. https://doi.org/10.1128/Mcb.01239-07
Article CAS PubMed PubMed Central Google Scholar
Ungermannova D, Lee J, Zhang G, Dallmann HG, McHenry CS, Liu XD (2013) High-throughput screening AlphaScreen assay for identification of small-molecule inhibitors of ubiquitin E3 ligase SCFSkp2-Cks1. J Biomol Screen 18(8):910–920. https://doi.org/10.1177/1087057113485789
Article CAS PubMed PubMed Central Google Scholar
van Duijn PW, Trapman J (2006) PI3K/Akt signaling regulates p27(kip) expression via Skp2 in PC3 and DU145 prostate cancer cells, but is not a major factor in p27(kip) regulation in LNCaP and PC346 cells. Prostate 66(7):749–760. https://doi.org/10.1002/pros.20398
Article CAS PubMed Google Scholar
Voduc D, Nielsen TO, Cheang MC, Foulkes WD (2008) The combination of high cyclin E and Skp2 expression in breast cancer is associated with a poor prognosis and the basal phenotype. Hum Pathol 39(10):1431–1437. https://doi.org/10.1016/j.humpath.2008.03.004
Article CAS PubMed Google Scholar
von der Lehr N, Johansson S, Wu S, Bahram F, Castell A, Cetinkaya C et al (2003) The F-box protein Skp2 participates in c-Myc proteosomal degradation and acts as a cofactor for c-Myc-regulated transcription. Mol Cell 11(5):1189–1200. https://doi.org/10.1016/S1097-2765(03)00193-X
Article PubMed Google Scholar
Wang HB, Sun DQ, Ji P, Mohler J, Zhu L (2008) An AR-Skp2 pathway for proliferation of androgen-dependent prostate-cancer cells. J Cell Sci 121(15):2578–2587. https://doi.org/10.1242/jcs.030742
Article CAS PubMed Google Scholar
Wang HB, Bauzon F, Ji P, Xu XL, Sun DQ, Locker J et al (2010) Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1(+/−) mice. Nat Genet 42(1):83–U105. https://doi.org/10.1038/ng.498
Article CAS PubMed Google Scholar
Wang J, Han F, Wu J, Lee SW, Chan CH, Wu CY et al (2011) The role of Skp2 in hematopoietic stem cell quiescence, pool size, and self-renewal. Blood 118(20):5429–5438. https://doi.org/10.1182/blood-2010-10-312785
Article PubMed PubMed Central Google Scholar
Wang J, Huang Y, Guan Z, Zhang JL, Su HK, Zhang W et al (2014b) E3-ligase Skp2 predicts poor prognosis and maintains cancer stem cell pool in nasopharyngeal carcinoma. Oncotarget 5(14):5591–5601. https://doi.org/10.18632/oncotarget.2149
Article PubMed PubMed Central Google Scholar
Wang SY, Garcia AJ, Wu M, Lawson DA, Witte ON, Wu H (2006) Pten deletion leads to the expansion of a prostatic stem/progenitor cell subpopulation and tumor initiation. Proc Natl Acad Sci U S A 103(5):1480–1485. https://doi.org/10.1073/pnas0510652103
Article CAS PubMed PubMed Central Google Scholar
Wang ZW, Gao DM, Fukushima H, Inuzuka H, Liu PD, Wan LX et al (2012) Skp2: a novel potential therapeutic target for prostate cancer. Biochim Biophys Acta 1825(1):11–17. https://doi.org/10.1016/j.bbcan.2011.09.002
Article CAS PubMed Google Scholar
Wang ZW, Liu PD, Inuzuka H, Wei WY (2014a) Roles of F-box proteins in cancer. Nat Rev Cancer 14(4):233–247. https://doi.org/10.1038/nrc3700
Article CAS PubMed PubMed Central Google Scholar
Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T et al (2004) M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCF beta-TrCP. Proc Natl Acad Sci USA 101(13):4419–4424. https://doi.org/10.1073/pnas.0307700101
Article CAS PubMed PubMed Central Google Scholar
Wei S, Yang HC, Chuang HC, Yang J, Kulp SK, Lu PJ et al (2008) A novel mechanism by which thiazolidinediones facilitate the proteasomal degradation of cyclin D1 in cancer cells. J Biol Chem 283(39):26759–26770. https://doi.org/10.1074/jbc.M802160200
Article CAS PubMed PubMed Central Google Scholar
Wei W, Ayad NG, Wan Y, Zhang G-J, Kirschner MW, Kaelin WG (2004) Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex. Nature 428(6979):194–198. https://doi.org/10.1038/nature02381
Article CAS PubMed Google Scholar
Wei WY, Jin JP, Schlisio S, Harper JW, Kaelin WG (2005) The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase. Cancer Cell 8(1):25–33. https://doi.org/10.1016/j.ccr.2005.06.005
Article CAS PubMed Google Scholar
Welcker M, Clurman BE (2008) FBW7 ubiquitin ligase: a tumour suppressor at the crossroads of cell division, growth and differentiation. Nat Rev Cancer 8(2):83–93. https://doi.org/10.1038/nrc2290
Article CAS PubMed Google Scholar
Welcker M, Larimore EA, Frappier L, Clurman BE (2011) Nucleolar targeting of the Fbw7 ubiquitin ligase by a pseudosubstrate and glycogen synthase kinase 3. Mol Cell Biol 31(6):1214–1224. https://doi.org/10.1128/Mcb.01347-10
Article CAS PubMed PubMed Central Google Scholar
Weng AP, Millholland JM, Yashiro-Ohtani Y, Arcangeli ML, Lau A, Wai C et al (2006) C-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev 20(15):2096–2109. https://doi.org/10.1101/gad.1450406
Article CAS PubMed PubMed Central Google Scholar
Wertz IE, Kusam S, Lam C, Okamoto T, Sandoval W, Anderson DJ et al (2011) Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7. Nature 471(7336):110–114. https://doi.org/10.1038/nature09779
Article CAS PubMed Google Scholar
Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ et al (2007) The genomic landscapes of human breast and colorectal cancers. Science 318(5853):1108–1113. https://doi.org/10.1126/science.1145720
Article CAS PubMed Google Scholar
Wu GY, Hubbard EJA, Kitajewski JK, Greenwald I (1998) Evidence for functional and physical association between Caenorhabditis elegans SEL-10, a Cdc4p-related protein, and SEL-12 presenilin. Proc Natl Acad Sci USA 95(26):15787–15791. https://doi.org/10.1073/pnas.95.26.15787
Article CAS PubMed PubMed Central Google Scholar
Wu L, Grigoryan AV, Li YF, Hao B, Pagano M, Cardozo TJ (2012) Specific small molecule inhibitors of Skp2-mediated p27 degradation. Chem Biol 19(12):1515–1524. https://doi.org/10.1016/j.chembiol.2012.09.015
Article CAS PubMed PubMed Central Google Scholar
Wu WJ, Shi J, Hu G, Yu X, Lu H, Yang ML et al (2016) Wnt/beta-catenin signaling inhibits FBXW7 expression by upregulation of microRNA-770 in hepatocellular carcinoma. Tumor Biol 37(5):6045–6051. https://doi.org/10.1007/s13277-015-4452-5
Article CAS Google Scholar
Xia W, Zhou JY, Luo HB, Liu YZ, Peng CC, Zheng WL et al (2017) MicroRNA-32 promotes cell proliferation, migration and suppresses apoptosis in breast cancer cells by targeting FBXW7. Cancer Cell Int 17. https://doi.org/10.1186/s12935-017-0383-0
Xia YF, Padre RC, De Mendoza TH, Bottero V, Tergaonkar VB, Verma IM (2009) Phosphorylation of p53 by I kappa B kinase 2 promotes its degradation by beta-TrCP. Proc Natl Acad Sci U S A 106(8):2629–2634. https://doi.org/10.1073/pnas.0812256106
Article PubMed PubMed Central Google Scholar
Xu J, Wu WB, Wang J, Huang CJ, Wen W, Zhao F et al (2017) miR-367 promotes the proliferation and invasion of non-small cell lung cancer via targeting FBXW7. Oncol Rep 37(2):1052–1058. https://doi.org/10.3892/or.2016.5314
Article CAS PubMed Google Scholar
Xu Y, Lee SH, Kim HS, Kim NH, Piao S, Park SH et al (2010b) Role of CK1 in GSK3 beta-mediated phosphorylation and degradation of snail. Oncogene 29(21):3124–3133. https://doi.org/10.1038/onc.2010.77
Article CAS PubMed Google Scholar
Xu YF, Sengupta T, Kukreja L, Minella AC (2010a) MicroRNA-223 regulates cyclin E activity by modulating expression of F-box and WD-40 domain protein 7. J Biol Chem 285(45):34439–34446. https://doi.org/10.1074/jbc.M110.152306
Article CAS PubMed PubMed Central Google Scholar
Yada M, Hatakeyama S, Kamura T, Nishiyama M, Tsunematsu R, Imaki H et al (2004) Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J 23(10):2116–2125. https://doi.org/10.1038/sj.emboj.7600217
Article CAS PubMed PubMed Central Google Scholar
Yang ES, Burnstein KL (2003) Vitamin D inhibits G(1) to S progression in LNCaP prostate cancer cells through p27(Kip1) stabilization and Cdk2 mislocalization to the cytoplasm. J Biol Chem 278(47):46862–46868. https://doi.org/10.1074/jbc.M306340200
Article CAS PubMed Google Scholar
Yang G, Ayala G, De Marzo A, Tian WH, Frolov A, Wheeler TM et al (2002) Elevated Skp2 protein expression in human prostate cancer: association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival. Clin Cancer Res 8(11):3419–3426
CAS PubMed Google Scholar
Yaron A, Hatzubai A, Davis M, Lavon I, Amit S, Manning AM et al (1998) Identification of the receptor component of the I kappa B alpha-ubiquitin ligase. Nature 396(6711):590–594. https://doi.org/10.1038/25159
Article CAS PubMed Google Scholar
Yokobori T, Mimori K, Iwatsuki M, Ishii H, Onoyama I, Fukagawa T et al (2009) p53-altered FBXW7 expression determines poor prognosis in gastric cancer cases. Cancer Res 69(9):3788–3794. https://doi.org/10.1158/0008-5472.CAN-08-2846
Article CAS PubMed Google Scholar
Yokoi S, Yasui K, Saito-Ohara F, Koshikawa K, Iizasa T, Fujisawa T et al (2002) A novel target gene, SKP2, within the 5p13 amplicon that is frequently detected in small cell lung cancers. Am J Pathol 161(1):207–216. https://doi.org/10.1016/S0002-9440(10)64172-7
Article CAS PubMed PubMed Central Google Scholar
Yu ZK, Gervais JLM, Zhang H (1998) Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21(CIP1/WAF1) and cyclin D proteins. Proc Natl Acad Sci U S A 95(19):11324–11329. https://doi.org/10.1073/pnas.95.19.11324
Article CAS PubMed PubMed Central Google Scholar
Zhan FH, Colla S, Wu XS, Chen BZ, Stewart JP, Kuehl WM et al (2007) CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27(Kip1)-dependent and -independent mechanisms. Blood 109(11):4995–5001. https://doi.org/10.1182/blood-2006-07-038703
Article CAS PubMed PubMed Central Google Scholar
Zhang L, Wang C (2006) F-box protein Skp2: a novel transcriptional target of E2F. Oncogene 25(18):2615–2627. https://doi.org/10.1038/sj.onc.1209286
Article CAS PubMed PubMed Central Google Scholar
Zhang W, MacDonald EM, Koepp DM (2012) The stomatin-like protein SLP-1 and Cdk2 interact with the F-box protein Fbw7-gamma. PLoS One 7(10). https://doi.org/10.1371/journal.pone.0047736
Article CAS PubMed PubMed Central Google Scholar
Zhao HL, Bauzon F, Fu H, Lu ZL, Cui JH, Nakayama K et al (2013) Skp2 deletion unmasks a p27 safeguard that blocks tumorigenesis in the absence of pRb and p53 tumor suppressors. Cancer Cell 24(5):645–659. https://doi.org/10.1016/j.ccr.2013.09.021
Article CAS PubMed Google Scholar
Zhao JZ, Hu CX, Chi JD, Li JS, Peng C, Yun XW et al (2016) miR-24 promotes the proliferation, migration and invasion in human tongue squamous cell carcinoma by targeting FBXW7. Oncol Rep 36(2):1143–1149. https://doi.org/10.3892/or.2016.4891
Article CAS PubMed Google Scholar
Zhao Y, Xiong X, Sun Y (2011) DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF βTrCP E3 ubiquitin ligase and regulates survival and autophagy. Mol Cell 44(2):304–316. https://doi.org/10.1016/j.molcel.2011.08.029
Article CAS PubMed PubMed Central Google Scholar
Zheng JY, Yang XM, Harrell JM, Ryzhikov S, Shim EH, Lykke-Andersen K et al (2002) CAND1 binds to unneddylated CUL1 and regulates the formation of SCF ubiquitin E3 ligase complex. Mol Cell 10(6):1519–1526. https://doi.org/10.1016/S1097-2765(02)00784-0
Article CAS PubMed Google Scholar
Zheng WQ, Zheng JM, Ma R, Meng FF, Ni CR (2005) Relationship between levels of Skp2 and P27 in breast carcinomas and possible role of Skp2 as targeted therapy. Steroids 70(11):770–774. https://doi.org/10.1016/j.steroids.2005.04.012
Article CAS PubMed Google Scholar
Zhou BHP, Deng J, Xia WY, Xu JH, Li YM, Gunduz M et al (2004) Dual regulation of snail by GSK-3 beta-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat Cell Biol 6(10):931–940. https://doi.org/10.1038/ncb1173
Article CAS PubMed Google Scholar
Zhu CQ, Blackhall FH, Pintilie M, Iyengar P, Liu N, Ho J et al (2004) Skp2 gene copy number aberrations are common in non-small cell lung carcinoma, and its overexpression in tumors with ras mutation is a poor prognostic marker. Clin Cancer Res 10(6):1984–1991. https://doi.org/10.1158/1078-0432.Ccr-03-0470
Article CAS PubMed Google Scholar
Zuo T, Liu RH, Zhang HM, Chang X, Liu Y, Wang LZ et al (2007a) FOXP3 is a novel transcriptional repressor for the breast cancer oncogene SKP2. J Clin Investig 117(12):3765–3773. https://doi.org/10.1172/JCI32538
Article CAS PubMed PubMed Central Google Scholar
Zuo T, Wang LZ, Morrison C, Chang X, Zhang HM, Li WQ et al (2007b) FOXP3 is an X-linked breast cancer suppressor gene and an important repressor of the HER-2/ErbB2 oncogene. Cell 129(7):1275–1286. https://doi.org/10.1016/j.cell.2007.04.034
Article CAS PubMed PubMed Central Google Scholar

Download references

Author information

Authors and Affiliations

Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, China
Jing Liu, Yunhua Peng, Jiangang Long & Jiankang Liu
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Yunhua Peng, Jinfang Zhang & Wenyi Wei

Authors

Jing Liu
View author publications
You can also search for this author in PubMed Google Scholar
Yunhua Peng
View author publications
You can also search for this author in PubMed Google Scholar
Jinfang Zhang
View author publications
You can also search for this author in PubMed Google Scholar
Jiangang Long
View author publications
You can also search for this author in PubMed Google Scholar
Jiankang Liu
View author publications
You can also search for this author in PubMed Google Scholar
Wenyi Wei
View author publications
You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jiankang Liu or Wenyi Wei .

Editor information

Editors and Affiliations

Radiation Oncology, University of Michigan, Ann Arbor, MI, USA
Yi Sun
Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
Wenyi Wei
Life Science Institute, Zhejiang University, Hangzhou, China
Jianping Jin

Rights and permissions

Reprints and permissions

Copyright information

About this chapter

Cite this chapter

Liu, J., Peng, Y., Zhang, J., Long, J., Liu, J., Wei, W. (2020). Targeting SCF E3 Ligases for Cancer Therapies. In: Sun, Y., Wei, W., Jin, J. (eds) Cullin-RING Ligases and Protein Neddylation. Advances in Experimental Medicine and Biology, vol 1217. Springer, Singapore. https://doi.org/10.1007/978-981-15-1025-0_9

Download citation

DOI: https://doi.org/10.1007/978-981-15-1025-0_9
Published: 03 January 2020
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-1024-3
Online ISBN: 978-981-15-1025-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

Publish with us

Policies and ethics