1932

Abstract

Uncontrolled cell proliferation and genomic instability are common features of cancer and can arise from, respectively, the loss of cell-cycle control and defective checkpoints. Ubiquitin-mediated proteolysis, ultimately executed by ubiquitin-ligating enzymes (E3s), plays a key part in cell-cycle regulation and is dominated by two multisubunit E3s, the anaphase-promoting complex (or cyclosome) (APC/C) and SKP1–cullin-1–F-box (SCF) complex. We highlight the role of APC/C and the SCF bound to F-box proteins, FBXW7, SKP2, and β-TrCP, in regulating the abundance of select fundamental proteins, primarily during the cell cycle, that are associated with human cancer. The clinical success of the first proteasome inhibitor, bortezomib, in treating multiple myeloma and mantle-cell lymphoma set the precedent for viewing the ubiquitin–proteasome system as a druggable target for cancer. Given that there are more E3s than kinases, selective, small-molecule E3 inhibitors have the potential of opening up another dimension in the therapeutic armamentarium for the treatment of cancer.

Keyword(s): APC/Ccancercell cycleE3proteasomeSCFubiquitin
Loading

Article metrics loading...

/content/journals/10.1146/annurev-cancerbio-040716-075607
2017-03-06
2024-06-24
Loading full text...

Full text loading...

/deliver/fulltext/cancerbio/1/1/annurev-cancerbio-040716-075607.html?itemId=/content/journals/10.1146/annurev-cancerbio-040716-075607&mimeType=html&fmt=ahah

Literature Cited

  1. Akhoondi S, Sun D, von der Lehr N, Apostolidou S, Klotz K. et al. 2007. FBXW7/hCDC4 is a general tumor suppressor in human cancer. Cancer Res 67:9006–12 [Google Scholar]
  2. Alexander K, Hinds PW. 2001. Requirement for p27KIP1 in retinoblastoma protein-mediated senescence. Mol. Cell. Biol. 21:3616–31 [Google Scholar]
  3. Bahram F, von der Lehr N, Cetinkaya C, Larsson LG. 2000. c-Myc hot spot mutations in lymphomas result in inefficient ubiquitination and decreased proteasome-mediated turnover. Blood 95:2104–10 [Google Scholar]
  4. Bailey P, Chang DK, Nones K, Johns AL, Patch AM. et al. 2016. Genomic analyses identify molecular subtypes of pancreatic cancer. Nature 531:47–52 [Google Scholar]
  5. Bashir T, Dorrello NV, Amador V, Guardavaccaro D, Pagano M. 2004. Control of the SCFSkp2-Cks1 ubiquitin ligase by the APC/CCdh1 ubiquitin ligase. Nature 428:190–93 [Google Scholar]
  6. Bassermann F, Frescas D, Guardavaccaro D, Busino L, Peschiaroli A, Pagano M. 2008. The Cdc14B–Cdh1–Plk1 axis controls the G2 DNA-damage-response checkpoint. Cell 134:256–67 [Google Scholar]
  7. Berlingieri MT, Pallante P, Sboner A, Barbareschi M, Bianco M. et al. 2007. UbcH10 is overexpressed in malignant breast carcinomas. Eur. J. Cancer 43:2729–35 [Google Scholar]
  8. Binne UK, Classon MK, Dick FA, Wei W, Rape M. et al. 2007. Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit. Nat. Cell Biol. 9:225–32 [Google Scholar]
  9. Bolesta E, Pfannenstiel LW, Demelash A, Lesniewski ML, Tobin M. et al. 2012. Inhibition of Mcl-1 promotes senescence in cancer cells: implications for preventing tumor growth and chemotherapy resistance. Mol. Cell. Biol. 32:1879–92 [Google Scholar]
  10. Brito DA, Rieder CL. 2006. Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint. Curr. Biol. 16:1194–200 [Google Scholar]
  11. Buschhorn BA, Petzold G, Galova M, Dube P, Kraft C. et al. 2011. Substrate binding on the APC/C occurs between the coactivator Cdh1 and the processivity factor Doc1. Nat. Struct. Mol. Biol. 18:6–13 [Google Scholar]
  12. Busino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D. et al. 2003. Degradation of Cdc25A by β-TrCP during S phase and in response to DNA damage. Nature 426:87–91 [Google Scholar]
  13. Buttyan R, Sawczuk IS, Benson MC, Siegal JD, Olsson CA. 1987. Enhanced expression of the c-myc protooncogene in high-grade human prostate cancers. Prostate 11:327–37 [Google Scholar]
  14. Carroll CW, Enquist-Newman M, Morgan DO. 2005. The APC subunit Doc1 promotes recognition of the substrate destruction box. Curr. Biol. 15:11–18 [Google Scholar]
  15. Carroll CW, Morgan DO. 2002. The Doc1 subunit is a processivity factor for the anaphase-promoting complex. Nat. Cell Biol. 4:880–87 [Google Scholar]
  16. Chan CH, Morrow JK, Li CF, Gao Y, Jin G. et al. 2013. Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression. Cell 154:556–68 [Google Scholar]
  17. Chang L, Zhang Z, Yang J, McLaughlin SH, Barford D. 2014. Molecular architecture and mechanism of the anaphase-promoting complex. Nature 513:388–93 [Google Scholar]
  18. Chao WC, Kulkarni K, Zhang Z, Kong EH, Barford D. 2012. Structure of the mitotic checkpoint complex. Nature 484:208–13 [Google Scholar]
  19. Chen SM, Jiang CY, Wu JY, Liu B, Chen YJ. et al. 2010. RNA interference-mediated silencing of UBCH10 gene inhibits colorectal cancer cell growth in vitro and in vivo. Clin. Exp. Pharmacol. Physiol. 37:525–29 [Google Scholar]
  20. Chuang SE, Yeh PY, Lu YS, Lai GM, Liao CM. et al. 2002. Basal levels and patterns of anticancer drug-induced activation of nuclear factor-κB (NF-κB), and its attenuation by tamoxifen, dexamethasone, and curcumin in carcinoma cells. Biochem. Pharmacol. 63:1709–16 [Google Scholar]
  21. Clurman BE, Sheaff RJ, Thress K, Groudine M, Roberts JM. 1996. Turnover of cyclin E by the ubiquitin–proteasome pathway is regulated by cdk2 binding and cyclin phosphorylation. Genes Dev. 10:1979–90 [Google Scholar]
  22. Clute P, Pines J. 1999. Temporal and spatial control of cyclin B1 destruction in metaphase. Nat. Cell Biol. 1:82–87 [Google Scholar]
  23. Fonseca PC, Kong EH, Zhang Z, Schreiber A, Williams MA. da et al. 2011. Structures of APC/CCdh1 with substrates identify Cdh1 and Apc10 as the D-box co-receptor. Nature 470:274–78 [Google Scholar]
  24. Diefenbacher ME, Popov N, Blake SM, Schulein-Volk C, Nye E. et al. 2014. The deubiquitinase USP28 controls intestinal homeostasis and promotes colorectal cancer. J. Clin. Investig. 124:3407–18 [Google Scholar]
  25. Ding Q, He X, Hsu JM, Xia W, Chen CT. et al. 2007. Degradation of Mcl-1 by β-TrCP mediates glycogen synthase kinase 3-induced tumor suppression and chemosensitization. Mol. Cell. Biol. 27:4006–17 [Google Scholar]
  26. Donzelli M, Busino L, Chiesa M, Ganoth D, Hershko A, Draetta GF. 2004. Hierarchical order of phosphorylation events commits Cdc25A to βTrCP-dependent degradation. Cell Cycle 3:469–71 [Google Scholar]
  27. Donzelli M, Squatrito M, Ganoth D, Hershko A, Pagano M, Draetta GF. 2002. Dual mode of degradation of Cdc25 A phosphatase. EMBO J. 21:4875–84 [Google Scholar]
  28. Engelbert D, Schnerch D, Baumgarten A, Wasch R. 2008. The ubiquitin ligase APCCdh1 is required to maintain genome integrity in primary human cells. Oncogene 27:907–17 [Google Scholar]
  29. Erlanson M, Portin C, Linderholm B, Lindh J, Roos G, Landberg G. 1998. Expression of cyclin E and the cyclin-dependent kinase inhibitor p27 in malignant lymphomas—prognostic implications. Blood 92:770–77 [Google Scholar]
  30. Eytan E, Sitry-Shevah D, Teichner A, Hershko A. 2013. Roles of different pools of the mitotic checkpoint complex and the mechanisms of their disassembly. PNAS 110:10568–73 [Google Scholar]
  31. Eytan E, Wang K, Miniowitz-Shemtov S, Sitry-Shevah D, Kaisari S. et al. 2014. Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31comet. PNAS 111:12019–24 [Google Scholar]
  32. Fang G, Yu H, Kirschner MW. 1998. Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. Mol. Cell 2:163–71 [Google Scholar]
  33. Fleming WH, Hamel A, MacDonald R, Ramsey E, Pettigrew NM. et al. 1986. Expression of the c-myc protooncogene in human prostatic carcinoma and benign prostatic hyperplasia. Cancer Res. 46:1535–38 [Google Scholar]
  34. Frost M, Newell J, Lones MA, Tripp SR, Cairo MS, Perkins SL. 2004. Comparative immunohistochemical analysis of pediatric Burkitt lymphoma and diffuse large B-cell lymphoma. Am. J. Clin. Pathol. 121:384–92 [Google Scholar]
  35. Frye JJ, Brown NG, Petzold G, Watson ER, Grace CR. et al. 2013. Electron microscopy structure of human APC/CCDH1-EMI1 reveals multimodal mechanism of E3 ligase shutdown. Nat. Struct. Mol. Biol. 20:827–35 [Google Scholar]
  36. Fukushima H, Ogura K, Wan L, Lu Y, Li V. et al. 2013. SCF-mediated Cdh1 degradation defines a negative feedback system that coordinates cell-cycle progression. Cell Rep. 4:803–16 [Google Scholar]
  37. Garcia-Higuera I, Manchado E, Dubus P, Canamero M, Mendez J. et al. 2008. Genomic stability and tumour suppression by the APC/C cofactor Cdh1. Nat. Cell Biol. 10:802–11 [Google Scholar]
  38. Garnett MJ, Mansfeld J, Godwin C, Matsusaka T, Wu J. et al. 2009. UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit. Nat. Cell Biol. 11:1363–69 [Google Scholar]
  39. Geley S, Kramer E, Gieffers C, Gannon J, Peters JM, Hunt T. 2001. Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint. J. Cell Biol. 153:137–48 [Google Scholar]
  40. Gerstein AV, Almeida TA, Zhao G, Chess E, Shih Ie M. et al. 2002. APC/CTNNB1 (β-catenin) pathway alterations in human prostate cancers. Genes Chromosom. Cancer 34:9–16 [Google Scholar]
  41. Golan A, Yudkovsky Y, Hershko A. 2002. The cyclin–ubiquitin ligase activity of cyclosome/APC is jointly activated by protein kinases Cdk1–cyclin B and Plk. J. Biol. Chem. 277:15552–57 [Google Scholar]
  42. Gregory MA, Hann SR. 2000. c-Myc proteolysis by the ubiquitin–proteasome pathway: stabilization of c-Myc in Burkitt's lymphoma cells. Mol. Cell. Biol. 20:2423–35 [Google Scholar]
  43. Greil C, Krohs J, Schnerch D, Follo M, Felthaus J. et al. 2016. The role of APC/CCdh1 in replication stress and origin of genomic instability. Oncogene 35:3062–70 [Google Scholar]
  44. Gstaiger M, Jordan R, Lim M, Catzavelos C, Mestan J. et al. 2001. Skp2 is oncogenic and overexpressed in human cancers. PNAS 98:5043–48 [Google Scholar]
  45. Guardavaccaro D, Kudo Y, Boulaire J, Barchi M, Busino L. et al. 2003. Control of meiotic and mitotic progression by the F box protein β-Trcp1 in vivo. Dev. Cell 4:799–812 [Google Scholar]
  46. Hagting A, Den Elzen N, Vodermaier HC, Waizenegger IC, Peters JM, Pines J. 2002. Human securin proteolysis is controlled by the spindle checkpoint and reveals when the APC/C switches from activation by Cdc20 to Cdh1. J. Cell Biol. 157:1125–37 [Google Scholar]
  47. Hansen DV, Loktev AV, Ban KH, Jackson PK. 2004. Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFβTrCP-dependent destruction of the APC inhibitor Emi1. Mol. Biol. Cell 15:5623–34 [Google Scholar]
  48. Harley ME, Allan LA, Sanderson HS, Clarke PR. 2010. Phosphorylation of Mcl-1 by CDK1–cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest. EMBO J. 29:2407–20 [Google Scholar]
  49. Hollstein M, Sidransky D, Vogelstein B, Harris CC. 1991. p53 mutations in human cancers. Science 253:49–53 [Google Scholar]
  50. Honaker Y, Piwnica-Worms H. 2010. Casein kinase 1 functions as both penultimate and ultimate kinase in regulating Cdc25A destruction. Oncogene 29:3324–34 [Google Scholar]
  51. Hsu JY, Reimann JD, Sorensen CS, Lukas J, Jackson PK. 2002. E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APCCdh1. Nat. Cell Biol. 4:358–66 [Google Scholar]
  52. Huang HC, Shi J, Orth JD, Mitchison TJ. 2009. Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer Cell 16:347–58 [Google Scholar]
  53. Inuzuka H, Shaik S, Onoyama I, Gao D, Tseng A. et al. 2011. SCFFBW7 regulates cellular apoptosis by targeting MCL1 for ubiquitylation and destruction. Nature 471:104–9 [Google Scholar]
  54. Inuzuka H, Tseng A, Gao D, Zhai B, Zhang Q. et al. 2010. Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCFβ-TRCP ubiquitin ligase. Cancer Cell 18:147–59 [Google Scholar]
  55. Jaspersen SL, Charles JF, Morgan DO. 1999. Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14. Curr. Biol. 9:227–36 [Google Scholar]
  56. Ji P, Jiang H, Rekhtman K, Bloom J, Ichetovkin M. et al. 2004. An Rb–Skp2–p27 pathway mediates acute cell cycle inhibition by Rb and is retained in a partial-penetrance Rb mutant. Mol. Cell 16:47–58 [Google Scholar]
  57. Jin J, Cardozo T, Lovering RC, Elledge SJ, Pagano M, Harper JW. 2004. Systematic analysis and nomenclature of mammalian F-box proteins. Genes Dev. 18:2573–80 [Google Scholar]
  58. Jin J, Shirogane T, Xu L, Nalepa G, Qin J. et al. 2003. SCFβ-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. Genes Dev. 17:3062–74 [Google Scholar]
  59. Jin L, Williamson A, Banerjee S, Philipp I, Rape M. 2008. Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell 133:653–65 [Google Scholar]
  60. Kaisari S, Sitry-Shevah D, Miniowitz-Shemtov S, Hershko A. 2016. Intermediates in the assembly of mitotic checkpoint complexes and their role in the regulation of the anaphase-promoting complex. PNAS 113:966–71 [Google Scholar]
  61. Kanemori Y, Uto K, Sagata N. 2005. β-TrCP recognizes a previously undescribed nonphosphorylated destruction motif in Cdc25A and Cdc25B phosphatases. PNAS 102:6279–84 [Google Scholar]
  62. Kim CJ, Song JH, Cho YG, Kim YS, Kim SY. et al. 2007. Somatic mutations of the β-TrCP gene in gastric cancer. APMIS 115:127–33 [Google Scholar]
  63. Kim CM, Koike K, Saito I, Miyamura T, Jay G. 1991. HBx gene of hepatitis B virus induces liver cancer in transgenic mice. Nature 351:317–20 [Google Scholar]
  64. Kim SY, Herbst A, Tworkowski KA, Salghetti SE, Tansey WP. 2003. Skp2 regulates Myc protein stability and activity. Mol. Cell 11:1177–88 [Google Scholar]
  65. Koch A, Waha A, Hartmann W, Hrychyk A, Schuller U. et al. 2005. Elevated expression of Wnt antagonists is a common event in hepatoblastomas. Clin. Cancer Res. 11:4295–304 [Google Scholar]
  66. Koepp DM, Schaefer LK, Ye X, Keyomarsi K, Chu C. et al. 2001. Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science 294:173–77 [Google Scholar]
  67. Komander D, Rape M. 2012. The ubiquitin code. Annu. Rev. Biochem. 81:203–29 [Google Scholar]
  68. Kraft C, Herzog F, Gieffers C, Mechtler K, Hagting A. et al. 2003. Mitotic regulation of the human anaphase-promoting complex by phosphorylation. EMBO J. 22:6598–609 [Google Scholar]
  69. Kramer ER, Scheuringer N, Podtelejnikov AV, Mann M, Peters JM. 2000. Mitotic regulation of the APC activator proteins CDC20 and CDH1. Mol. Biol. Cell 11:1555–69 [Google Scholar]
  70. Kumagai A, Lee J, Yoo HY, Dunphy WG. 2006. TopBP1 activates the ATR–ATRIP complex. Cell 124:943–55 [Google Scholar]
  71. Lafranchi L, de Boer HR, de Vries EG, Ong SE, Sartori AA, van Vugt MA. 2014. APC/CCdh1 controls CtIP stability during the cell cycle and in response to DNA damage. EMBO J. 33:2860–79 [Google Scholar]
  72. Lee S, Kim W, Ko C, Ryu WS. 2016. Hepatitis B virus X protein enhances Myc stability by inhibiting SCFSkp2 ubiquitin E3 ligase-mediated Myc ubiquitination and contributes to oncogenesis. Oncogene 35:1857–67 [Google Scholar]
  73. Lehman NL, Verschuren EW, Hsu JY, Cherry AM, Jackson PK. 2006. Overexpression of the anaphase promoting complex/cyclosome inhibitor Emi1 leads to tetraploidy and genomic instability of p53-deficient cells. Cell Cycle 5:1569–73 [Google Scholar]
  74. Leverson JD, Zhang H, Chen J, Tahir SK, Phillips DC. et al. 2015. Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Cell Death Dis. 6e1590 [Google Scholar]
  75. Li M, Fang X, Wei Z, York JP, Zhang P. 2009. Loss of spindle assembly checkpoint-mediated inhibition of Cdc20 promotes tumorigenesis in mice. J. Cell Biol. 185:983–94 [Google Scholar]
  76. Li SZ, Song Y, Zhang HH, Jin BX, Liu Y. et al. 2014. UbcH10 overexpression increases carcinogenesis and blocks ALLN susceptibility in colorectal cancer. Sci. Rep. 4:6910 [Google Scholar]
  77. Li VS, Ng SS, Boersema PJ, Low TY, Karthaus WR. et al. 2012. Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex. Cell 149:1245–56 [Google Scholar]
  78. Li W, Bengtson MH, Ulbrich A, Matsuda A, Reddy VA. et al. 2008. Genome-wide and functional annotation of human E3 ubiquitin ligases identifies MULAN, a mitochondrial E3 that regulates the organelle's dynamics and signaling. PLOS ONE 3e1487 [Google Scholar]
  79. Lin HK, Chen Z, Wang G, Nardella C, Lee SW. et al. 2010. Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature 464:374–79 [Google Scholar]
  80. Lindsey-Boltz LA, Sancar A. 2011. Tethering DNA damage checkpoint mediator proteins topoisomerase IIβ-binding protein 1 (TopBP1) and Claspin to DNA activates ataxia-telangiectasia mutated and RAD3-related (ATR) phosphorylation of checkpoint kinase 1 (Chk1). J. Biol. Chem. 286:19229–36 [Google Scholar]
  81. Listovsky T, Oren YS, Yudkovsky Y, Mahbubani HM, Weiss AM. et al. 2004. Mammalian Cdh1/Fzr mediates its own degradation. EMBO J. 23:1619–26 [Google Scholar]
  82. Liu J, Suresh Kumar KG, Yu D, Molton SA, McMahon M. et al. 2007. Oncogenic BRAF regulates β-Trcp expression and NF-κB activity in human melanoma cells. Oncogene 26:1954–58 [Google Scholar]
  83. Mailand N, Bekker-Jensen S, Bartek J, Lukas J. 2006. Destruction of Claspin by SCFβTrCP restrains Chk1 activation and facilitates recovery from genotoxic stress. Mol. Cell 23:307–18 [Google Scholar]
  84. Malempati S, Tibbitts D, Cunningham M, Akkari Y, Olson S. et al. 2006. Aberrant stabilization of c-Myc protein in some lymphoblastic leukemias. Leukemia 20:1572–81 [Google Scholar]
  85. Malureanu L, Jeganathan KB, Jin F, Baker DJ, van Ree JH. et al. 2010. Cdc20 hypomorphic mice fail to counteract de novo synthesis of cyclin B1 in mitosis. J. Cell Biol. 191:313–29 [Google Scholar]
  86. Mamely I, van Vugt MA, Smits VA, Semple JI, Lemmens B. et al. 2006. Polo-like kinase-1 controls proteasome-dependent degradation of Claspin during checkpoint recovery. Curr. Biol. 16:1950–55 [Google Scholar]
  87. Margottin-Goguet F, Hsu JY, Loktev A, Hsieh HM, Reimann JD, Jackson PK. 2003. Prophase destruction of Emi1 by the SCFβTrCP/Slimb ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Dev. Cell 4:813–26 [Google Scholar]
  88. Matsumoto ML, Wickliffe KE, Dong KC, Yu C, Bosanac I. et al. 2010. K11-linked polyubiquitination in cell cycle control revealed by a K11 linkage-specific antibody. Mol. Cell 39:477–84 [Google Scholar]
  89. Matsuoka S, Oike Y, Onoyama I, Iwama A, Arai F. et al. 2008. Fbxw7 acts as a critical fail-safe against premature loss of hematopoietic stem cells and development of T-ALL. Genes Dev. 22:986–91 [Google Scholar]
  90. Matyskiela ME, Morgan DO. 2009. Analysis of activator-binding sites on the APC/C supports a cooperative substrate-binding mechanism. Mol. Cell 34:68–80 [Google Scholar]
  91. Meyer HJ, Rape M. 2014. Enhanced protein degradation by branched ubiquitin chains. Cell 157:910–21 [Google Scholar]
  92. Miller JJ, Summers MK, Hansen DV, Nachury MV, Lehman NL. et al. 2006. Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor. Genes Dev. 20:2410–20 [Google Scholar]
  93. Minella AC, Loeb KR, Knecht A, Welcker M, Varnum-Finney BJ. et al. 2008. Cyclin E phosphorylation regulates cell proliferation in hematopoietic and epithelial lineages in vivo. Genes Dev. 22:1677–89 [Google Scholar]
  94. Miniowitz-Shemtov S, Eytan E, Kaisari S, Sitry-Shevah D, Hershko A. 2015. Mode of interaction of TRIP13 AAA-ATPase with the Mad2-binding protein p31comet and with mitotic checkpoint complexes. PNAS 112:11536–40 [Google Scholar]
  95. Moshe Y, Boulaire J, Pagano M, Hershko A. 2004. Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome. PNAS 101:7937–42 [Google Scholar]
  96. Muerkoster S, Arlt A, Sipos B, Witt M, Grossmann M. et al. 2005. Increased expression of the E3-ubiquitin ligase receptor subunit βTRCP1 relates to constitutive nuclear factor-κB activation and chemoresistance in pancreatic carcinoma cells. Cancer Res. 65:1316–24 [Google Scholar]
  97. Onoyama I, Tsunematsu R, Matsumoto A, Kimura T, de Alboran IM. et al. 2007. Conditional inactivation of Fbxw7 impairs cell-cycle exit during T cell differentiation and results in lymphomatogenesis. J. Exp. Med. 204:2875–88 [Google Scholar]
  98. Ougolkov A, Zhang B, Yamashita K, Bilim V, Mai M. et al. 2004. Associations among β-TrCP, an E3 ubiquitin ligase receptor, β-catenin, and NF-κB in colorectal cancer. J. Natl. Cancer Inst. 96:1161–70 [Google Scholar]
  99. Passmore LA, McCormack EA, Au SW, Paul A, Willison KR. et al. 2003. Doc1 mediates the activity of the anaphase-promoting complex by contributing to substrate recognition. EMBO J. 22:786–96 [Google Scholar]
  100. Pavelka N, Rancati G, Li R. 2010. Dr Jekyll and Mr Hyde: role of aneuploidy in cellular adaptation and cancer. Curr. Opin. Cell Biol. 22:809–15 [Google Scholar]
  101. Peschiaroli A, Dorrello NV, Guardavaccaro D, Venere M, Halazonetis T. et al. 2006. SCFβTrCP-mediated degradation of Claspin regulates recovery from the DNA replication checkpoint response. Mol. Cell 23:319–29 [Google Scholar]
  102. Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV. et al. 2007. Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Hum. Mutat. 28:622–29 [Google Scholar]
  103. Popov N, Wanzel M, Madiredjo M, Zhang D, Beijersbergen R. et al. 2007. The ubiquitin-specific protease USP28 is required for MYC stability. Nat. Cell Biol. 9:765–74 [Google Scholar]
  104. Rajagopalan H, Jallepalli PV, Rago C, Velculescu VE, Kinzler KW. et al. 2004. Inactivation of hCDC4 can cause chromosomal instability. Nature 428:77–81 [Google Scholar]
  105. Rape M, Kirschner MW. 2004. Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry. Nature 432:588–95 [Google Scholar]
  106. Reimann JD, Freed E, Hsu JY, Kramer ER, Peters JM, Jackson PK. 2001a. Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Cell 105:645–55 [Google Scholar]
  107. Reimann JD, Gardner BE, Margottin-Goguet F, Jackson PK. 2001b. Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins. Genes Dev. 15:3278–85 [Google Scholar]
  108. Roberts JR, Allison DC, Donehower RC, Rowinsky EK. 1990. Development of polyploidization in taxol-resistant human leukemia cells in vitro. Cancer Res. 50:710–16 [Google Scholar]
  109. Sackton KL, Dimova N, Zeng X, Tian W, Zhang M. et al. 2014. Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C. Nature 514:646–49 [Google Scholar]
  110. Saitoh T, Katoh M. 2001. Expression profiles of βTRCP1 and βTRCP2, and mutation analysis of βTRCP2 in gastric cancer. Int. J. Oncol. 18:959–64 [Google Scholar]
  111. Salghetti SE, Kim SY, Tansey WP. 1999. Destruction of Myc by ubiquitin-mediated proteolysis: cancer-associated and transforming mutations stabilize Myc. EMBO J. 18:717–26 [Google Scholar]
  112. Schulein-Volk C, Wolf E, Zhu J, Xu W, Taranets L. et al. 2014. Dual regulation of Fbw7 function and oncogenic transformation by Usp28. Cell Rep. 9:1099–109 [Google Scholar]
  113. Shieh SY, Ahn J, Tamai K, Taya Y, Prives C. 2000. The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev. 14:289–300 [Google Scholar]
  114. Sigl R, Wandke C, Rauch V, Kirk J, Hunt T, Geley S. 2009. Loss of the mammalian APC/C activator FZR1 shortens G1 and lengthens S phase but has little effect on exit from mitosis. J. Cell Sci. 122:4208–17 [Google Scholar]
  115. Sistrunk C, Kim SH, Wang X, Lee SH, Kim Y. et al. 2013. Skp2 deficiency inhibits chemical skin tumorigenesis independent of p27Kip1 accumulation. Am. J. Pathol. 182:1854–64 [Google Scholar]
  116. Skaar JR, Pagan JK, Pagano M. 2013. Mechanisms and function of substrate recruitment by F-box proteins. Nat. Rev. Mol. Cell Biol. 14:369–81 [Google Scholar]
  117. Spruck CH, Won KA, Reed SI. 1999. Deregulated cyclin E induces chromosome instability. Nature 401:297–300 [Google Scholar]
  118. 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 413:316–22 [Google Scholar]
  119. Sudo T, Nitta M, Saya H, Ueno NT. 2004. Dependence of paclitaxel sensitivity on a functional spindle assembly checkpoint. Cancer Res. 64:2502–8 [Google Scholar]
  120. Sudo T, Ota Y, Kotani S, Nakao M, Takami Y. et al. 2001. Activation of Cdh1-dependent APC is required for G1 cell cycle arrest and DNA damage-induced G2 checkpoint in vertebrate cells. EMBO J. 20:6499–508 [Google Scholar]
  121. Tan Y, Sangfelt O, Spruck C. 2008. The Fbxw7/hCdc4 tumor suppressor in human cancer. Cancer Lett. 271:1–12 [Google Scholar]
  122. Thompson BJ, Buonamici S, Sulis ML, Palomero T, Vilimas T. et al. 2007. The SCFFBW7 ubiquitin ligase complex as a tumor suppressor in T cell leukemia. J. Exp. Med. 204:1825–35 [Google Scholar]
  123. Timofeev O, Cizmecioglu O, Hu E, Orlik T, Hoffmann I. 2009. Human Cdc25A phosphatase has a non-redundant function in G2 phase by activating Cyclin A-dependent kinases. FEBS Lett. 583:841–47 [Google Scholar]
  124. van Ree JH, Jeganathan KB, Malureanu L, van Deursen JM. 2010. Overexpression of the E2 ubiquitin-conjugating enzyme UbcH10 causes chromosome missegregation and tumor formation. J. Cell Biol. 188:83–100 [Google Scholar]
  125. von der Lehr N, Johansson S, Wu S, Bahram F, Castell A. 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 11:1189–200 [Google Scholar]
  126. Wang CY, Cusack JC Jr., Liu R, Baldwin AS Jr. 1999. Control of inducible chemoresistance: enhanced anti-tumor therapy through increased apoptosis by inhibition of NF-κB. Nat. Med. 5:412–17 [Google Scholar]
  127. Wang CY, Mayo MW, Baldwin AS Jr. 1996. TNF- and cancer therapy-induced apoptosis: potentiation by inhibition of NF-κB. Science 274:784–87 [Google Scholar]
  128. Wang H, Bauzon F, Ji P, Xu X, Sun D. et al. 2010. Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/− mice. Nat. Genet. 42:83–88 [Google Scholar]
  129. Wang K, Yuen ST, Xu J, Lee SP, Yan HH. et al. 2014a. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat. Genet. 46:573–82 [Google Scholar]
  130. Wang L, Liu X, Gusev E, Wang C, Fagotto F. 2014b. Regulation of the phosphorylation and nuclear import and export of β-catenin by APC and its cancer-related truncated form. J. Cell Sci. 127:1647–59 [Google Scholar]
  131. Wang Q, Moyret-Lalle C, Couzon F, Surbiguet-Clippe C, Saurin JC. et al. 2003. Alterations of anaphase-promoting complex genes in human colon cancer cells. Oncogene 22:1486–90 [Google Scholar]
  132. Wang W, Kirschner MW. 2013. Emi1 preferentially inhibits ubiquitin chain elongation by the anaphase-promoting complex. Nat. Cell Biol. 15:797–806 [Google Scholar]
  133. Wang Z, Inuzuka H, Zhong J, Fukushima H, Wan L. et al. 2012. DNA damage-induced activation of ATM promotes β-TRCP-mediated Mdm2 ubiquitination and destruction. Oncotarget 3:1026–35 [Google Scholar]
  134. Warr MR, Acoca S, Liu Z, Germain M, Watson M. et al. 2005. BH3-ligand regulates access of MCL-1 to its E3 ligase. FEBS Lett. 579:5603–8 [Google Scholar]
  135. Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N. et al. 2004. M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFβ-TrCP. PNAS 101:4419–24 [Google Scholar]
  136. Wei W, Ayad NG, Wan Y, Zhang GJ, Kirschner MW, Kaelin WG Jr. 2004. Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex. Nature 428:194–98 [Google Scholar]
  137. Welcker M, Orian A, Jin J, Grim JE, Harper JW. et al. 2004. The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. PNAS 101:9085–90 [Google Scholar]
  138. Welcker M, Singer J, Loeb KR, Grim J, Bloecher A. et al. 2003. Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol. Cell 12:381–92 [Google Scholar]
  139. Wertz IE, Kusam S, Lam C, Okamoto T, Sandoval W. et al. 2011. Sensitivity to antitubulin chemotherapeutics is regulated by MCL1 and FBW7. Nature 471:110–14 [Google Scholar]
  140. Williamson A, Wickliffe KE, Mellone BG, Song L, Karpen GH, Rape M. 2009. Identification of a physiological E2 module for the human anaphase-promoting complex. PNAS 106:18213–18 [Google Scholar]
  141. Wolf F, Wandke C, Isenberg N, Geley S. 2006. Dose-dependent effects of stable cyclin B1 on progression through mitosis in human cells. EMBO J. 25:2802–13 [Google Scholar]
  142. Won KA, Reed SI. 1996. Activation of cyclin E/CDK2 is coupled to site-specific autophosphorylation and ubiquitin-dependent degradation of cyclin E. EMBO J. 15:4182–93 [Google Scholar]
  143. Wu T, Merbl Y, Huo Y, Gallop JL, Tzur A, Kirschner MW. 2010. UBE2S drives elongation of K11-linked ubiquitin chains by the anaphase-promoting complex. PNAS 107:1355–60 [Google Scholar]
  144. Xiao Z, Chen Z, Gunasekera AH, Sowin TJ, Rosenberg SH. et al. 2003. Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents. J. Biol. Chem. 278:21767–73 [Google Scholar]
  145. Yada M, Hatakeyama S, Kamura T, Nishiyama M, Tsunematsu R. et al. 2004. Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J. 23:2116–25 [Google Scholar]
  146. Yuan X, Srividhya J, De Luca T, Lee JH, Pomerening JR. 2014. Uncovering the role of APC-Cdh1 in generating the dynamics of S-phase onset. Mol. Biol. Cell 25:441–56 [Google Scholar]
  147. Zachariae W, Schwab M, Nasmyth K, Seufert W. 1998. Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the anaphase promoting complex. Science 282:1721–24 [Google Scholar]
  148. Zhang D, Zaugg K, Mak TW, Elledge SJ. 2006. A role for the deubiquitinating enzyme USP28 in control of the DNA-damage response. Cell 126:529–42 [Google Scholar]
  149. Zhao H, Bauzon F, Fu H, Lu Z, Cui J. et al. 2013. Skp2 deletion unmasks a p27 safeguard that blocks tumorigenesis in the absence of pRb and p53 tumor suppressors. Cancer Cell 24:645–59 [Google Scholar]
  150. Zhong Q, Gao W, Du F, Wang X. 2005. Mule/ARF-BP1, a BH3-only E3 ubiquitin ligase, catalyzes the polyubiquitination of Mcl-1 and regulates apoptosis. Cell 121:1085–95 [Google Scholar]
/content/journals/10.1146/annurev-cancerbio-040716-075607
Loading
/content/journals/10.1146/annurev-cancerbio-040716-075607
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error