Small molecule therapeutics targeting F-box proteins in cancer

Seminars in Cancer Biology - Tập 36 - Trang 105-119 - 2016
Yuan Liu1, Rama K. Mallampalli1,2
1Department of Medicine, The Acute Lung Injury, Center of Excellence, University of Pittsburgh, Pittsburgh, PA 15213, United States
2Medical Specialty Service Line, Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, PA 15240, United States

Tài liệu tham khảo

Stockwell, 2011, Outsmarting Cancer. A biologist talks about what makes disease-causing proteins so difficult to target with drugs, Sci. Am., 305, 20 Hershko, 1998, The ubiquitin system, Ann. Rev. Biochem., 67, 425, 10.1146/annurev.biochem.67.1.425 Komander, 2012, The ubiquitin code, Ann. Rev. Biochem., 81, 203, 10.1146/annurev-biochem-060310-170328 Deshaies, 2009, RING domain E3 ubiquitin ligases, Ann. Rev. Biochem., 78, 399, 10.1146/annurev.biochem.78.101807.093809 Petroski, 2005, Function and regulation of cullin–RING ubiquitin ligases, Nat. Rev. Mol. Cell Biol., 6, 9, 10.1038/nrm1547 Feldman, 1997, A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p, Cell, 91, 221, 10.1016/S0092-8674(00)80404-3 Skowyra, 1997, F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin–ligase complex, Cell, 91, 209, 10.1016/S0092-8674(00)80403-1 Cardozo, 2004, The SCF ubiquitin ligase: insights into a molecular machine, Nat. Rev. Mol. Cell Biol., 5, 739, 10.1038/nrm1471 Bai, 1996, SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box, Cell, 86, 263, 10.1016/S0092-8674(00)80098-7 Cenciarelli, 1999, Identification of a family of human F-box proteins, Curr. Biol.: CB, 9, 1177, 10.1016/S0960-9822(00)80020-2 Winston, 1999, A family of mammalian F-box proteins, Curr. Biol.: CB, 9, 1180, 10.1016/S0960-9822(00)80021-4 Jin, 2004, Systematic analysis and nomenclature of mammalian F-box proteins, Genes Dev., 18, 2573, 10.1101/gad.1255304 Ravid, 2008, Diversity of degradation signals in the ubiquitin-proteasome system, Nat. Rev. Mol. Cell Biol., 9, 679, 10.1038/nrm2468 Lau, 2012, The Fbw7 and betaTRCP E3 ubiquitin ligases and their roles in tumorigenesis, Front. Biosci., 17, 2197, 10.2741/4045 Frescas, 2008, Deregulated proteolysis by the F-box proteins SKP2 and beta-TrCP: tipping the scales of cancer, Nat. Rev. Cancer, 8, 438, 10.1038/nrc2396 Nash, 2001, Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication, Nature, 414, 514, 10.1038/35107009 Liu, 2002, Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism, Cell, 108, 837, 10.1016/S0092-8674(02)00685-2 Welcker, 2003, Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation, Mol. Cell, 12, 381, 10.1016/S1097-2765(03)00287-9 Wei, 2005, The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase, Cancer Cell, 8, 25, 10.1016/j.ccr.2005.06.005 Abbas, 2013, CRL1-FBXO11 promotes Cdt2 ubiquitylation and degradation and regulates Pr-Set7/Set8-mediated cellular migration, Mol. Cell, 49, 1147, 10.1016/j.molcel.2013.02.003 Rossi, 2013, Regulation of the CRL4(Cdt2) ubiquitin ligase and cell-cycle exit by the SCF(Fbxo11) ubiquitin ligase, Mol. Cell, 49, 1159, 10.1016/j.molcel.2013.02.004 Skaar, 2013, Mechanisms and function of substrate recruitment by F-box proteins, Nat. Rev. Mol. Cell Biol., 14, 369, 10.1038/nrm3582 D’Angiolella, 2010, SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation, Nature, 466, 138, 10.1038/nature09140 Chen, 2011, Calmodulin antagonizes a calcium-activated SCF ubiquitin E3 ligase subunit, FBXL2, to regulate surfactant homeostasis, Mol. Cell. Biol., 31, 1905, 10.1128/MCB.00723-10 Chen, 2012, F-box protein FBXL2 exerts human lung tumor suppressor-like activity by ubiquitin-mediated degradation of cyclin D3 resulting in cell cycle arrest, Oncogene, 31, 2566, 10.1038/onc.2011.432 Chen, 2012, F-box protein FBXL2 targets cyclin D2 for ubiquitination and degradation to inhibit leukemic cell proliferation, Blood, 119, 3132, 10.1182/blood-2011-06-358911 D’Angiolella, 2012, Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair, Cell, 149, 1023, 10.1016/j.cell.2012.03.043 Chen, 2013, A combinatorial F box protein directed pathway controls TRAF adaptor stability to regulate inflammation, Nat. Immunol., 14, 470, 10.1038/ni.2565 Liu, 2015, F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7, Cell Death Dis., 6, e1630, 10.1038/cddis.2014.585 Richardson, 2003, A phase 2 study of bortezomib in relapsed, refractory myeloma, N. Engl. J. Med., 348, 2609, 10.1056/NEJMoa030288 Richardson, 2006, Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib, J. Clin. Oncol.: Off. J. Am. Soc. Clin. Oncol., 24, 3113, 10.1200/JCO.2005.04.7779 Kouroukis, 2014, Bortezomib in multiple myeloma: systematic review and clinical considerations, Curr. Oncol., 21, e573, 10.3747/co.21.1798 Xie, 2013, Role of SKP1-CUL1-F-box-protein (SCF) E3 ubiquitin ligases in skin cancer, J. Genet. Genom. – Yi chuan xue bao, 40, 97, 10.1016/j.jgg.2013.02.001 Zhao, 2013, Cullin–RING Ligases as attractive anti-cancer targets, Curr. Pharm. Des., 19, 3215, 10.2174/13816128113199990300 Weathington, 2014, Emerging therapies targeting the ubiquitin proteasome system in cancer, J. Clin. Invest., 124, 6, 10.1172/JCI71602 Skaar, 2014, SCF ubiquitin ligase-targeted therapies, Nat. Rev. Drug Discov., 13, 889, 10.1038/nrd4432 Wang, 2014, Roles of F-box proteins in cancer, Nat. Rev. Cancer, 14, 233, 10.1038/nrc3700 Liu, 2015, Targeting the ubiquitin pathway for cancer treatment, Biochim. Biophys. Acta, 1855, 50 Yu, 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, 11324, 10.1073/pnas.95.19.11324 Tsvetkov, 1999, p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27, Curr. Biol.: CB, 9, 661, 10.1016/S0960-9822(99)80290-5 Sutterluty, 1999, p45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells, Nat. Cell Biol., 1, 207, 10.1038/12027 Carrano, 1999, SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27, Nat. Cell Biol., 1, 193, 10.1038/12013 Ganoth, 2001, The cell-cycle regulatory protein Cks1 is required for SCF(Skp2)-mediated ubiquitinylation of p27, Nat. Cell Biol., 3, 321, 10.1038/35060126 Spruck, 2001, A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1, Mol. Cell, 7, 639, 10.1016/S1097-2765(01)00210-6 Nakayama, 2004, Skp2-mediated degradation of p27 regulates progression into mitosis, Dev. Cell, 6, 661, 10.1016/S1534-5807(04)00131-5 Kossatz, 2004, Skp2-dependent degradation of p27kip1 is essential for cell cycle progression, Genes Dev., 18, 2602, 10.1101/gad.321004 Chan, 2013, Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression, Cell, 154, 556, 10.1016/j.cell.2013.06.048 Chan, 2012, The Skp2-SCF E3 ligase regulates Akt ubiquitination, glycolysis, herceptin sensitivity, and tumorigenesis, Cell, 149, 1098, 10.1016/j.cell.2012.02.065 Chen, 2008, Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy, Blood, 111, 4690, 10.1182/blood-2007-09-112904 Nickeleit, 2008, Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition, Cancer Cell, 14, 23, 10.1016/j.ccr.2008.05.016 Rico-Bautista, 2010, Chemical genetics approach to restoring p27Kip1 reveals novel compounds with antiproliferative activity in prostate cancer cells, BMC Biol., 8, 153, 10.1186/1741-7007-8-153 Wu, 2012, Specific small molecule inhibitors of Skp2-mediated p27 degradation, Chem. Biol., 19, 1515, 10.1016/j.chembiol.2012.09.015 Yang, 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.: Off. J. Am. Assoc. Cancer Res., 8, 3419 Liu, 2009, p27-Associated G1 arrest induced by hinokitiol in human malignant melanoma cells is mediated via down-regulation of pRb, Skp2 ubiquitin ligase, and impairment of Cdk2 function, Cancer Lett., 286, 240, 10.1016/j.canlet.2009.05.038 Koga, 2003, Troglitazone induces p27Kip1-associated cell-cycle arrest through down-regulating Skp2 in human hepatoma cells, Hepatology, 37, 1086, 10.1053/jhep.2003.50186 Hsieh, 2012, Prodigiosin down-regulates SKP2 to induce p27(KIP1) stabilization and antiproliferation in human lung adenocarcinoma cells, Br. J. Pharmacol., 166, 2095, 10.1111/j.1476-5381.2012.01921.x Chung, 2015, Sulforaphane down-regulates SKP2 to stabilize p27(KIP1) for inducing antiproliferation in human colon adenocarcinoma cells, J. Biosci. Bioeng., 119, 35, 10.1016/j.jbiosc.2014.06.009 Sumimoto, 2006, Effective inhibition of cell growth and invasion of melanoma by combined suppression of BRAF (V599E) and Skp2 with lentiviral RNAi, Int. J. Cancer, 118, 472, 10.1002/ijc.21286 Wang, 2007, Prognostic significance of nuclear ING3 expression in human cutaneous melanoma, Clin. Cancer Res.: Off. J. Am. Assoc. Cancer Res., 13, 4111, 10.1158/1078-0432.CCR-07-0408 Chen, 2010, The tumor suppressor ING3 is degraded by SCF(Skp2)-mediated ubiquitin-proteasome system, Oncogene, 29, 1498, 10.1038/onc.2009.424 Fuchs, 2004, The many faces of beta-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer, Oncogene, 23, 2028, 10.1038/sj.onc.1207389 Perkins, 2007, Integrating cell-signalling pathways with NF-kappaB and IKK function, Nat. Rev. Mol. Cell Biol., 8, 49, 10.1038/nrm2083 Chen, 2005, Ubiquitin signalling in the NF-kappaB pathway, Nat. Cell Biol., 7, 758, 10.1038/ncb0805-758 Yaron, 1998, Identification of the receptor component of the IkappaBalpha-ubiquitin ligase, Nature, 396, 590, 10.1038/25159 Nakajima, 2008, A novel small-molecule inhibitor of NF-kappaB signaling, Biochem. Biophys. Res. Commun., 368, 1007, 10.1016/j.bbrc.2008.01.166 Nakayama, 2003, Impaired degradation of inhibitory subunit of NF-κB (IκB) and β-catenin as a result of targeted disruption of the β-TrCP1 gene, Proc. Natl. Acad. Sci., 100, 8752, 10.1073/pnas.1133216100 Yang, 2003, The transformation suppressor Pdcd4 is a novel eukaryotic translation initiation factor 4A binding protein that inhibits translation, Mol. Cell. Biol., 23, 26, 10.1128/MCB.23.1.26-37.2003 Mudduluru, 2007, Loss of programmed cell death 4 expression marks adenoma-carcinoma transition, correlates inversely with phosphorylated protein kinase B, and is an independent prognostic factor in resected colorectal cancer, Cancer, 110, 1697, 10.1002/cncr.22983 Wei, 2009, Loss of Programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer, Mol. Cancer, 8, 70, 10.1186/1476-4598-8-70 Dorrello, 2006, S6K1- and betaTRCP-mediated degradation of PDCD4 promotes protein translation and cell growth, Science, 314, 467, 10.1126/science.1130276 Blees, 2012, Erioflorin stabilizes the tumor suppressor Pdcd4 by inhibiting its interaction with the E3-ligase beta-TrCP1, PloS ONE, 7, e46567, 10.1371/journal.pone.0046567 Peterson, 2009, DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival, Cell, 137, 873, 10.1016/j.cell.2009.03.046 Duan, 2011, mTOR generates an auto-amplification loop by triggering the betaTrCP- and CK1alpha-dependent degradation of DEPTOR, Mol. Cell, 44, 317, 10.1016/j.molcel.2011.09.005 Gao, 2011, mTOR drives its own activation via SCF(betaTrCP)-dependent degradation of the mTOR inhibitor DEPTOR, Mol. Cell, 44, 290, 10.1016/j.molcel.2011.08.030 Zhao, 2011, DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(betaTrCP) E3 ubiquitin ligase and regulates survival and autophagy, Mol. Cell, 44, 304, 10.1016/j.molcel.2011.08.029 Boyd, 2010, High expression levels of the mammalian target of rapamycin inhibitor DEPTOR are predictive of response to thalidomide in myeloma, Leuk. Lymphoma, 51, 2126, 10.3109/10428194.2010.509893 Sakamoto, 2001, Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation, Proc. Natl. Acad. Sci. U.S.A., 98, 8554, 10.1073/pnas.141230798 Sakamoto, 2003, Development of Protacs to target cancer-promoting proteins for ubiquitination and degradation, Mol. Cell. Proteomics: MCP, 2, 1350, 10.1074/mcp.T300009-MCP200 Schneekloth, 2008, Targeted intracellular protein degradation induced by a small molecule: En route to chemical proteomics, Bioorgan. Med. Chem. Lett., 18, 5904, 10.1016/j.bmcl.2008.07.114 O’Connor, 1998, Bim: a novel member of the Bcl-2 family that promotes apoptosis, EMBO J., 17, 384, 10.1093/emboj/17.2.384 Fletcher, 2008, Controlling the cell death mediators Bax and Bak: puzzles and conundrums, Cell Cycle, 7, 39, 10.4161/cc.7.1.5178 Dehan, 2009, betaTrCP- and Rsk1/2-mediated degradation of BimEL inhibits apoptosis, Mol. Cell, 33, 109, 10.1016/j.molcel.2008.12.020 Rogers, 2009, The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication, J. Cell Biol., 184, 225, 10.1083/jcb.200808049 Cunha-Ferreira, 2009, The SCF/Slimb ubiquitin ligase limits centrosome amplification through degradation of SAK/PLK4, Curr. Biol.: CB, 19, 43, 10.1016/j.cub.2008.11.037 Akhoondi, 2007, FBXW7/hCDC4 is a general tumor suppressor in human cancer, Cancer Res., 67, 9006, 10.1158/0008-5472.CAN-07-1320 Spruck, 2011, miR-27a regulation of SCF(Fbw7) in cell division control and cancer, Cell Cycle, 10, 3232, 10.4161/cc.10.19.17125 Ma, 2013, Genistein down-regulates miR-223 expression in pancreatic cancer cells, Curr. Drug Targets, 14, 1150, 10.2174/13894501113149990187 Kimura, 2003, hCDC4b, a regulator of cyclin E, as a direct transcriptional target of p53, Cancer Sci., 94, 431, 10.1111/j.1349-7006.2003.tb01460.x Mao, 2004, Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene, Nature, 432, 775, 10.1038/nature03155 Balamurugan, 2010, The tumour suppressor C/EBPdelta inhibits FBXW7 expression and promotes mammary tumour metastasis, EMBO J., 29, 4106, 10.1038/emboj.2010.280 Welcker, 2004, The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation, Proc. Natl. Acad. Sci. U.S.A., 101, 9085, 10.1073/pnas.0402770101 von der Lehr, 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, 1189, 10.1016/S1097-2765(03)00193-X Kim, 2003, Skp2 regulates Myc protein stability and activity, Mol. Cell, 11, 1177, 10.1016/S1097-2765(03)00173-4 Yada, 2004, Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7, EMBO J., 23, 2116, 10.1038/sj.emboj.7600217 Zhou, 2007, Back to the future of oridonin: again, compound from medicinal herb shows potent antileukemia efficacies in vitro and in vivo, Cell Res., 17, 274, 10.1038/cr.2007.21 Huang, 2012, Triggering Fbw7-mediated proteasomal degradation of c-Myc by oridonin induces cell growth inhibition and apoptosis, Mol. Cancer Ther., 11, 1155, 10.1158/1535-7163.MCT-12-0066 Xia, 2012, Genistein inhibits cell growth and induces apoptosis through up-regulation of miR-34a in pancreatic cancer cells, Curr. Drug Targets, 13, 1750, 10.2174/138945012804545597 Reavie, 2013, Regulation of c-Myc ubiquitination controls chronic myelogenous leukemia initiation and progression, Cancer Cell, 23, 362, 10.1016/j.ccr.2013.01.025 Gregory, 2000, c-Myc proteolysis by the ubiquitin-proteasome pathway: stabilization of c-Myc in Burkitt's lymphoma cells, Mol. Cell. Biol., 20, 2423, 10.1128/MCB.20.7.2423-2435.2000 Busino, 2012, Fbxw7alpha- and GSK3-mediated degradation of p100 is a pro-survival mechanism in multiple myeloma, Nat. Cell Biol., 14, 375, 10.1038/ncb2463 Inoue, 2000, Tumor necrosis factor receptor-associated factor (TRAF) family: adapter proteins that mediate cytokine signaling, Exp. Cell Res., 254, 14, 10.1006/excr.1999.4733 Mallampalli, 2013, Targeting F box protein Fbxo3 to control cytokine-driven inflammation, J. Immunol., 191, 5247, 10.4049/jimmunol.1300456 Chen, 2013, Skp-cullin-F box E3 ligase component FBXL2 ubiquitinates Aurora B to inhibit tumorigenesis, Cell Death Dis., 4, e759, 10.1038/cddis.2013.271 Margolis, 2005, Tetraploidy and tumor development, Cancer Cell, 8, 353, 10.1016/j.ccr.2005.10.017 Fujiwara, 2005, Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells, Nature, 437, 1043, 10.1038/nature04217 Cimini, 2006, Aurora kinase promotes turnover of kinetochore microtubules to reduce chromosome segregation errors, Curr. Biol.: CB, 16, 1711, 10.1016/j.cub.2006.07.022 Coon, 2012, Novel E3 ligase component FBXL7 ubiquitinates and degrades Aurora A, causing mitotic arrest, Cell Cycle, 11, 721, 10.4161/cc.11.4.19171 Liu, 2015, The proapoptotic F-box protein Fbxl7 regulates mitochondrial function by mediating the ubiquitylation and proteasomal degradation of survivin, J. Biol. Chem., 290, 11843, 10.1074/jbc.M114.629931 Johansson, 2014, SCF-FBXO31 E3 ligase targets DNA replication factor Cdt1 for proteolysis in the G2 phase of cell cycle to prevent re-replication, J. Biol. Chem., 289, 18514, 10.1074/jbc.M114.559930 Santra, 2009, F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage, Nature, 459, 722, 10.1038/nature08011 Lin, 2006, Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF (FBX4-alphaB crystallin) complex, Mol. Cell, 24, 355, 10.1016/j.molcel.2006.09.007 Wade, 2013, MDM2, MDMX and p53 in oncogenesis and cancer therapy, Nat. Rev. Cancer, 13, 83, 10.1038/nrc3430 Malonia, 2015, F-box protein FBXO31 directs degradation of MDM2 to facilitate p53-mediated growth arrest following genotoxic stress, Proc. Natl. Acad. Sci. U.S.A., 112, 8632, 10.1073/pnas.1510929112 Huang, 2015, FBXO31 promotes cell proliferation, metastasis and invasion in lung cancer, Am. J. Cancer Res., 5, 1814 Liu, 2014, F-box only protein 31 (FBXO31) negatively regulates p38 mitogen-activated protein kinase (MAPK) signaling by mediating lysine 48-linked ubiquitination and degradation of mitogen-activated protein kinase kinase 6 (MKK6), J. Biol. Chem., 289, 21508, 10.1074/jbc.M114.560342 Fung, 2002, Cyclin F is degraded during G2-M by mechanisms fundamentally different from other cyclins, J. Biol. Chem., 277, 35140, 10.1074/jbc.M205503200 Nordlund, 2006, Ribonucleotide reductases, Ann. Rev. Biochem., 75, 681, 10.1146/annurev.biochem.75.103004.142443 Fu, 2013, Low cyclin F expression in hepatocellular carcinoma associates with poor differentiation and unfavorable prognosis, Cancer Sci., 104, 508, 10.1111/cas.12100 Ci, 2008, B-cell lymphoma 6 and the molecular pathogenesis of diffuse large B-cell lymphoma, Curr. Opin. Hematol., 15, 381, 10.1097/MOH.0b013e328302c7df Staudt, 2005, The biology of human lymphoid malignancies revealed by gene expression profiling, Adv. Immunol., 87, 163, 10.1016/S0065-2776(05)87005-1 Duan, 2012, FBXO11 targets BCL6 for degradation and is inactivated in diffuse large B-cell lymphomas, Nature, 481, 90, 10.1038/nature10688 Higa, 2006, L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and regulates CDT1 proteolysis in response to DNA damage, Cell Cycle, 5, 1675, 10.4161/cc.5.15.3149 Abbas, 2010, CRL4(Cdt2) regulates cell proliferation and histone gene expression by targeting PR-Set7/Set8 for degradation, Mol. Cell, 40, 9, 10.1016/j.molcel.2010.09.014 Centore, 2010, CRL4(Cdt2)-mediated destruction of the histone methyltransferase Set8 prevents premature chromatin compaction in S phase, Mol. Cell, 40, 22, 10.1016/j.molcel.2010.09.015 Oda, 2010, Regulation of the histone H4 monomethylase PR-Set7 by CRL4(Cdt2)-mediated PCNA-dependent degradation during DNA damage, Mol. Cell, 40, 364, 10.1016/j.molcel.2010.10.011 Havens, 2011, Mechanism of CRL4(Cdt2), a PCNA-dependent E3 ubiquitin ligase, Genes Dev., 25, 1568, 10.1101/gad.2068611 Jorgensen, 2011, SET8 is degraded via PCNA-coupled CRL4(CDT2) ubiquitylation in S phase and after UV irradiation, J. Cell Biol., 192, 43, 10.1083/jcb.201009076 Hall, 2014, C/EBPalpha regulates CRL4(Cdt2)-mediated degradation of p21 in response to UVB-induced DNA damage to control the G1/S checkpoint, Cell Cycle, 13, 3602, 10.4161/15384101.2014.962957 Pan, 2006, Role of L2DTL, cell cycle-regulated nuclear and centrosome protein, in aggressive hepatocellular carcinoma, Cell Cycle, 5, 2676, 10.4161/cc.5.22.3500 Ueki, 2008, Involvement of elevated expression of multiple cell-cycle regulator DTL/RAMP (denticleless/RA-regulated nuclear matrix associated protein), in the growth of breast cancer cells, Oncogene, 27, 5672, 10.1038/onc.2008.186 Yang, 2015, The oncogenic microRNA-21 inhibits the tumor suppressive activity of FBXO11 to promote tumorigenesis, J. Biol. Chem., 290, 6037, 10.1074/jbc.M114.632125 Xue, 2015, MiRNA-621 sensitizes breast cancer to chemotherapy by suppressing FBXO11 and enhancing p53 activity, Oncogene Dias, 2002, CUL7: A DOC domain-containing cullin selectively binds Skp1 Fbx29 to form an SCF-like complex, Proc. Natl. Acad. Sci. U.S.A., 99, 16601, 10.1073/pnas.252646399 Tsunematsu, 2006, Fbxw8 is essential for Cul1–Cul7 complex formation and for placental development, Mol. Cell. Biol., 26, 6157, 10.1128/MCB.00595-06 Okabe, 2006, A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation, PloS ONE, 1, e128, 10.1371/journal.pone.0000128 Kong, 2012, Ubiquitination and degradation of the hominoid-specific oncoprotein TBC1D3 is mediated by CUL7 E3 ligase, PloS ONE, 7, e46485, 10.1371/journal.pone.0046485 Wang, 2014, The CUL7/F-box and WD repeat domain containing 8 (CUL7/Fbxw8) ubiquitin ligase promotes degradation of hematopoietic progenitor kinase 1, J. Biol. Chem., 289, 4009, 10.1074/jbc.M113.520106 Takai, 2007, Tel2 regulates the stability of PI3K-related protein kinases, Cell, 131, 1248, 10.1016/j.cell.2007.10.052 Horejsi, 2010, CK2 phospho-dependent binding of R2TP complex to TEL2 is essential for mTOR and SMG1 stability, Mol. Cell, 39, 839, 10.1016/j.molcel.2010.08.037 Takai, 2010, Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes, Genes Dev., 24, 2019, 10.1101/gad.1956410 Kaizuka, 2010, Tti1 and Tel2 are critical factors in mammalian target of rapamycin complex assembly, J. Biol. Chem., 285, 20109, 10.1074/jbc.M110.121699 Fernandez-Saiz, 2013, SCFFbxo9 and CK2 direct the cellular response to growth factor withdrawal via Tel2/Tti1 degradation and promote survival in multiple myeloma, Nat. Cell Biol., 15, 72, 10.1038/ncb2651 Kim, 2013, CRL4A-FBXW5-mediated degradation of DLC1 Rho GTPase-activating protein tumor suppressor promotes non-small cell lung cancer cell growth, Proc. Natl. Acad. Sci. U.S.A., 110, 16868, 10.1073/pnas.1306358110 Hsu, 2002, E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APCCdh1, Nat. Cell Biol., 4, 358, 10.1038/ncb785 Gutgemann, 2008, Emi1 protein accumulation implicates misregulation of the anaphase promoting complex/cyclosome pathway in ovarian clear cell carcinoma, Mod. Pathol., 21, 445, 10.1038/modpathol.3801022 Huang, 2011, 1,2,3,4,6-penta-O-galloyl-beta-d-glucose, quercetin, curcumin and lycopene induce cell-cycle arrest in MDA-MB-231 and BT474 cells through downregulation of Skp2 protein, J. Agric. Food Chem., 59, 6765, 10.1021/jf201096v Huang, 2008, EGCG stabilizes p27kip1 in E2-stimulated MCF-7 cells through down-regulation of the Skp2 protein, Endocrinology, 149, 5972, 10.1210/en.2008-0408 Yang, 2003, Vitamin D inhibits G1 to S progression in LNCaP prostate cancer cells through p27Kip1 stabilization and Cdk2 mislocalization to the cytoplasm, J. Biol. Chem., 278, 46862, 10.1074/jbc.M306340200 Gao, 2014, Nuclear retention of Fbw7 by specific inhibitors of nuclear export leads to Notch1 degradation in pancreatic cancer, Oncotarget, 5, 3444, 10.18632/oncotarget.1813 Huang, 2012, Triggering Fbw7-mediated proteasomal degradation of c-Myc by oridonin induces cell growth inhibition and apoptosis, Mol. Cancer Ther., 11, 1155, 10.1158/1535-7163.MCT-12-0066 Nangle, 2013, Crystal structure of mammalian cryptochrome in complex with a small molecule competitor of its ubiquitin ligase, Cell Res., 23, 1417, 10.1038/cr.2013.136 Hirota, 2012, Identification of small molecule activators of cryptochrome, Science, 337, 1094, 10.1126/science.1223710 Lagarou, 2008, dKDM2 couples histone H2A ubiquitylation to histone H3 demethylation during Polycomb group silencing, Genes Dev., 22, 2799, 10.1101/gad.484208 Tzatsos, 2013, KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs, J. Clin. Invest., 123, 727 Xiao, 2015, FBXL20-mediated Vps34 ubiquitination as a p53 controlled checkpoint in regulating autophagy and receptor degradation, Genes Dev., 29, 184, 10.1101/gad.252528.114 Takagi, 2012, SCRAPPER Regulates the Thresholds of Long-Term Potentiation/Depression, the Bidirectional Synaptic Plasticity in Hippocampal CA3-CA1 Synapses, Neural Plast., 2012, 7, 10.1155/2012/352829 Dobie, 2007, A fight for neurotransmission: SCRAPPER trashes RIM, Cell, 130, 775, 10.1016/j.cell.2007.08.020 Yao, 2007, SCRAPPER-dependent ubiquitination of active zone protein RIM1 regulates synaptic vesicle release, Cell, 130, 943, 10.1016/j.cell.2007.06.052 Zhu, 2012, Role of FBXL20 in human colorectal adenocarcinoma, Oncol. Rep., 28, 2290, 10.3892/or.2012.2065 Zhu, 2014, FBXL20 acts as an invasion inducer and mediates E-cadherin in colorectal adenocarcinoma, Oncol. Lett., 7, 2185, 10.3892/ol.2014.2031 Huber, 2005, Identification of mutations in CUL7 in 3-M syndrome, Nat. Genet., 37, 1119, 10.1038/ng1628 Ponyeam, 2012, Characterization of the Cullin7 E3 ubiquitin ligase – heterodimerization of cullin substrate receptors as a novel mechanism to regulate cullin E3 ligase activity, Cell. Signal., 24, 290, 10.1016/j.cellsig.2011.08.020 Okabe, 2006, A critical role for FBXW8 and MAPK in cyclin D1 degradation and cancer cell proliferation, PloS ONE, 1, e128, 10.1371/journal.pone.0000128 Xu, 2008, The CUL7 E3 ubiquitin ligase targets insulin receptor substrate 1 for ubiquitin-dependent degradation, Mol. Cell, 30, 403, 10.1016/j.molcel.2008.03.009 Litterman, 2011, An OBSL1-Cul7Fbxw8 ubiquitin ligase signaling mechanism regulates golgi morphology and dendrite patterning, PLoS Biol., 9, e1001060, 10.1371/journal.pbio.1001060 Barbash, 2008, Mutations in Fbx4 inhibit dimerization of the SCFFbx4 ligase and contribute to cyclin D1 overexpression in human cancer, Cancer Cell, 14, 68, 10.1016/j.ccr.2008.05.017 Lin, 2006, Phosphorylation-dependent ubiquitination of cyclin D1 by the SCFFBX4-αB crystallin complex, Mol. Cell, 24, 355, 10.1016/j.molcel.2006.09.007 Koepp, 2001, Phosphorylation-dependent ubiquitination of cyctin E by the SCFFbw7 ubiquitin ligase, Science, 294, 173, 10.1126/science.1065203 Lee, 2006, The F-box protein FBX4 targets PIN2/TRF1 for ubiquitin-mediated degradation and regulates telomere maintenance, J. Biol. Chem., 281, 759, 10.1074/jbc.M509855200 Chen, 2011, Bcr-Abl-induced tyrosine phosphorylation of Emi1 to stabilize Skp2 protein via inhibition of ubiquitination in chronic myeloid leukemia cells, J. Cell. Physiol., 226, 407, 10.1002/jcp.22346 Lehman, 2007, Oncogenic regulators and substrates of the anaphase promoting complex/cyclosome are frequently overexpressed in malignant tumors, Am. J. Pathol., 170, 1793, 10.2353/ajpath.2007.060767 Fernández-Sáiz, 2013, SCFFbxo9 and CK2 direct the cellular response to growth factor withdrawal via Tel2/Tti1 degradation and promote survival in multiple myeloma, Nat. Cell Biol., 15, 72, 10.1038/ncb2651 Smits, 2012, An insulator loop resides between the synthetically interacting elements of the human/rat conserved breast cancer susceptibility locus MCS5A/Mcs5a, Nucleic Acids Res., 40, 132, 10.1093/nar/gkr610 Xu, 2014, Human MCS5A1 candidate breast cancer susceptibility gene FBXO10 is induced by cellular stress and correlated with lens epithelium-derived growth factor (LEDGF), Mol. Carcinog., 53, 300, 10.1002/mc.21977 Samuelson, 2007, Rat Mcs5a is a compound quantitative trait locus with orthologous human loci that associate with breast cancer risk, Proc. Natl. Acad. Sci., 104, 6299, 10.1073/pnas.0701687104 Zheng, 2014, PKD1 phosphorylation-dependent degradation of SNAIL by SCF-FBXO11 regulates epithelial-mesenchymal transition and metastasis, Cancer Cell, 26, 358, 10.1016/j.ccr.2014.07.022 Jeong, 2013, FBH1 protects melanocytes from transformation and is deregulated in melanomas, Cell Cycle, 12, 1128, 10.4161/cc.24165 Jeong, 2013, FBH1 promotes DNA double-strand breakage and apoptosis in response to DNA replication stress, J. Cell Biol., 200, 141, 10.1083/jcb.201209002 Fugger, 2009, Human Fbh1 helicase contributes to genome maintenance via pro- and anti-recombinase activities, J. Cell Biol., 186, 655, 10.1083/jcb.200812138 Huang, 2010, FBXO31 is down-regulated and may function as a tumor suppressor in hepatocellular carcinoma, Oncol. Rep., 24, 715 Kogo, 2011, FBXO31 determines poor prognosis in esophageal squamous cell carcinoma, Int. J. Oncol., 39, 155