Skp2 Deletion Unmasks a p27 Safeguard that Blocks Tumorigenesis in the Absence of pRb and p53 Tumor Suppressors

Cancer Cell

Volumn 24, Issue 5, 2013, Pages 645-659

  Zhao, Hongling ^a   Bauzon, Frederick ^a   Fu, Hao ^a   Lu, Zhonglei ^a   Cui, Jinhua ^a   Nakayama, Keiko ^b   Nakayama, Keiich I ^c   Locker, Joseph ^d   Zhu, Liang ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^b TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^c KYUSHU UNIVERSITY   (Japan)

^d UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEIN P27; PROTEIN P53; RETINOBLASTOMA PROTEIN; S PHASE KINASE ASSOCIATED PROTEIN 2; UBIQUITIN PROTEIN LIGASE; UBIQUITIN PROTEIN LIGASE KPC1; UBIQUITIN PROTEIN LIGASE PIRH2; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CANCER CELL CULTURE; CARCINOGENESIS; CELL LABELING; CONTROLLED STUDY; DNA REPLICATION; DNA REREPLICATION; DNA SYNTHESIS; EMBRYO; HUMAN; HUMAN CELL; HYPOPHYSIS CARCINOGENESIS; MITOSIS INHIBITION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROSTATE CARCINOGENESIS; PROSTATIC INTRAEPITHELIAL NEOPLASIA; PROTEIN DEPLETION; PROTEIN EXPRESSION; PROTEIN FUNCTION;

EID: 84887560579     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccr.2013.09.021     Document Type: Article

References (46)

1. Arias E.E., Walter J.C. Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells. Genes Dev. 2007, 21:497-518.
2. Balthasar N., Coppari R., McMinn J., Liu S.M., Lee C.E., Tang V., Kenny C.D., McGovern R.A., Chua S.C., Elmquist J.K., Lowell B.B. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 2004, 42:983-991.
3. Berman S.D., Calo E., Landman A.S., Danielian P.S., Miller E.S., West J.C., Fonhoue B.D., Caron A., Bronson R., Bouxsein M.L., et al. Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage. Proc. Natl. Acad. Sci. USA 2008, 105:11851-11856.
4. Burkhart D.L., Sage J. Cellular mechanisms of tumour suppression by the retinoblastoma gene. Nat. Rev. Cancer 2008, 8:671-682.
5. Cao X., Xue L., Han L., Ma L., Chen T., Tong T. WW domain-containing E3 ubiquitin protein ligase 1 (WWP1) delays cellular senescence by promoting p27(Kip1) degradation in human diploid fibroblasts. J.Biol. Chem. 2011, 286:33447-33456.
6. Ceccarelli D.F., Tang X., Pelletier B., Orlicky S., Xie W., Plantevin V., Neculai D., Chou Y.C., Ogunjimi A., Al-Hakim A., et al. An allosteric inhibitor of the human Cdc34 ubiquitin-conjugating enzyme. Cell 2011, 145:1075-1087.
7. Chan C.H., Morrow J.K., Li C.F., Gao Y., Jin G., Moten A., Stagg L.J., Ladbury J.E., Cai Z., Xu D., et al. Pharmacological inactivation of Skp2 SCF ubiquitin ligase restricts cancer stem cell traits and cancer progression. Cell 2013, 154:556-568.
8. Chen Q., Xie W., Kuhn D.J., Voorhees P.M., Lopez-Girona A., Mendy D., Corral L.G., Krenitsky V.P., Xu W., Moutouh-de Parseval L., et al. Targeting the p27 E3 ligase SCF(Skp2) results in p27- and Skp2-mediated cell-cycle arrest and activation of autophagy. Blood 2008, 111:4690-4699.
9. Chicas A., Wang X., Zhang C., McCurrach M., Zhao Z., Mert O., Dickins R.A., Narita M., Zhang M., Lowe S.W. Dissecting the unique role of the retinoblastoma tumor suppressor during cellular senescence. Cancer Cell 2010, 17:376-387.
10. Ciechanover A. Proteolysis: from the lysosome to ubiquitin and the proteasome. Nat. Rev. Mol. Cell Biol. 2005, 6:79-87.
11. Coppé J.P., Desprez P.Y., Krtolica A., Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu. Rev. Pathol. 2010, 5:99-118.
12. el-Deiry W.S., Kern S.E., Pietenpol J.A., Kinzler K.W., Vogelstein B. Definition of a consensus binding site for p53. Nat. Genet. 1992, 1:45-49.
13. Fero M.L., Rivkin M., Tasch M., Porter P., Carow C.E., Firpo E., Polyak K., Tsai L.-H., Broudy V., Perlmutter R.M., et al. A syndrome of multiorgan hyperplasia with features of gigantism, tumorigenesis, and female sterility in p27(Kip1)-deficient mice. Cell 1996, 85:733-744.
14. Flesken-Nikitin A., Choi K.C., Eng J.P., Shmidt E.N., Nikitin A.Y. Induction of carcinogenesis by concurrent inactivation of p53 and Rb1 in the mouse ovarian surface epithelium. Cancer Res. 2003, 63:3459-3463.
15. Hattori T., Isobe T., Abe K., Kikuchi H., Kitagawa K., Oda T., Uchida C., Kitagawa M. Pirh2 promotes ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor p27Kip1. Cancer Res. 2007, 67:10789-10795.
16. Jackson J.G., Pant V., Li Q., Chang L.L., Quintás-Cardama A., Garza D., Tavana O., Yang P., Manshouri T., Li Y., et al. p53-mediated senescence impairs the apoptotic response to chemotherapy and clinical outcome in breast cancer. Cancer Cell 2012, 21:793-806.
17. Jiang Z., Deng T., Jones R., Li H., Herschkowitz J.I., Liu J.C., Weigman V.J., Tsao M.S., Lane T.F., Perou C.M., Zacksenhaus E. Rb deletion in mouse mammary progenitors induces luminal-B or basal-like/EMT tumor subtypes depending on p53 status. J.Clin. Invest. 2010, 120:3296-3309.
18. Jonkers J., Meuwissen R., van der Gulden H., Peterse H., van der Valk M., Berns A. Synergistic tumor suppressor activity of BRCA2 and p53 in a conditional mouse model for breast cancer. Nat. Genet. 2001, 29:418-425.
19. Kamura T., Hara T., Matsumoto M., Ishida N., Okumura F., Hatakeyama S., Yoshida M., Nakayama K., Nakayama K.I. Cytoplasmic ubiquitin ligase KPC regulates proteolysis of p27(Kip1) at G1 phase. Nat. Cell Biol. 2004, 6:1229-1235.
20. Kang T.W., Yevsa T., Woller N., Hoenicke L., Wuestefeld T., Dauch D., Hohmeyer A., Gereke M., Rudalska R., Potapova A., et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature 2011, 479:547-551.
21. Kiyokawa H., Kineman R.D., Manova-Todorova K.O., Soares V.C., Hoffman E.S., Ono M., Khanam D., Hayday A.C., Frohman L.A., Koff A. Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27(Kip1). Cell 1996, 85:721-732.
22. Krtolica A., Parrinello S., Lockett S., Desprez P.Y., Campisi J. Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging. Proc. Natl. Acad. Sci. USA 2001, 98:12072-12077.
23. Kuilman T., Peeper D.S. Senescence-messaging secretome: SMS-ing cellular stress. Nat. Rev. Cancer 2009, 9:81-94.
24. Leng R.P., Lin Y., Ma W., Wu H., Lemmers B., Chung S., Parant J.M., Lozano G., Hakem R., Benchimol S. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell 2003, 112:779-791.
25. Lin H.K., Chen Z., Wang G., Nardella C., Lee S.W., Chan C.H., Yang W.L., Wang J., Egia A., Nakayama K.I., et al. Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature 2010, 464:374-379.
26. Marino S., Vooijs M., van Der Gulden H., Jonkers J., Berns A. Induction of medulloblastomas in p53-null mutant mice by somatic inactivation of Rb in the external granular layer cells of the cerebellum. Genes Dev. 2000, 14:994-1004.
27. McClendon A.K., Dean J.L., Ertel A., Fu Z., Rivadeneira D.B., Reed C.A., Bourgo R.J., Witkiewicz A., Addya S., Mayhew C.N., et al. RB and p53 cooperate to prevent liver tumorigenesis in response to tissue damage. Gastroenterology 2011, 141:1439-1450.
28. Meuwissen R., Linn S.C., Linnoila R.I., Zevenhoven J., Mooi W.J., Berns A. Induction of small cell lung cancer by somatic inactivation of both Trp53 and Rb1 in a conditional mouse model. Cancer Cell 2003, 4:181-189.
29. Nakayama K., Ishida N., Shirane M., Inomata A., Inoue T., Shishido N., Horii I., Loh D.Y., Nakayama K.-i. Mice lacking p27(Kip1) display increased body size, multiple organ hyperplasia, retinal dysplasia, and pituitary tumors. Cell 1996, 85:707-720.
30. Nakayama K., Nagahama H., Minamishima Y.A., Matsumoto M., Nakamichi I., Kitagawa K., Shirane M., Tsunematsu R., Tsukiyama T.I., Ishida N., et al. Targeted disruption of Skp2 results in accumulation of cyclin E and p27(Kip1), polyploidy and centrosome overduplication. EMBO J. 2000, 19:2069-2081.
31. Nakayama K., Nagahama H., Minamishima Y.A., Miyake S., Ishida N., Hatakeyama S., Kitagawa M., Iemura S., Natsume T., Nakayama K.I. Skp2-mediated degradation of p27 regulates progression into mitosis. Dev. Cell 2004, 6:661-672.
32. Nickeleit I., Zender S., Sasse F., Geffers R., Brandes G., Sörensen I., Steinmetz H., Kubicka S., Carlomagno T., Menche D., et al. Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition. Cancer Cell 2008, 14:23-35.
33. Old J.B., Kratzat S., Hoellein A., Graf S., Nilsson J.A., Nilsson L., Nakayama K.I., Peschel C., Cleveland J.L., Keller U.B. Skp2 directs Myc-mediated suppression of p27Kip1 yet has modest effects on Myc-driven lymphomagenesis. Mol. Cancer Res. 2010, 8:353-362.
34. Park J.H., Walls J.E., Galvez J.J., Kim M., Abate-Shen C., Shen M.M., Cardiff R.D. Prostatic intraepithelial neoplasia in genetically engineered mice. Am. J. Pathol. 2002, 161:727-735.
35. Sage J., Miller A.L., Pérez-Mancera P.A., Wysocki J.M., Jacks T. Acute mutation of retinoblastoma gene function is sufficient for cell cycle re-entry. Nature 2003, 424:223-228.
36. Sherr C.J. Ink4-Arf locus in cancer and aging. Wiley interdisciplinary reviews. Dev. Biol. 2012, 1:731-741.
37. Soucy T.A., Smith P.G., Milhollen M.A., Berger A.J., Gavin J.M., Adhikari S., Brownell J.E., Burke K.E., Cardin D.P., Critchley S., et al. An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer. Nature 2009, 458:732-736.
38. Sun D., Melegari M., Sridhar S., Rogler C.E., Zhu L. Multi-miRNA hairpin method that improves gene knockdown efficiency and provides linked multi-gene knockdown. Biotechniques 2006, 41:59-63.
39. Walkley C.R., Qudsi R., Sankaran V.G., Perry J.A., Gostissa M., Roth S.I., Rodda S.J., Snay E., Dunning P., Fahey F.H., et al. Conditional mouse osteosarcoma, dependent on p53 loss and potentiated by loss of Rb, mimics the human disease. Genes Dev. 2008, 22:1662-1676.
40. Wang H., Bauzon F., Ji P., Xu X., Sun D., Locker J., Sellers R.S., Nakayama K., Nakayama K.I., Cobrinik D., Zhu L. Skp2 is required for survival of aberrantly proliferating Rb1-deficient cells and for tumorigenesis in Rb1+/- mice. Nat. Genet. 2010, 42:83-88.
41. Wei C.L., Wu Q., Vega V.B., Chiu K.P., Ng P., Zhang T., Shahab A., Yong H.C., Fu Y., Weng Z., et al. A global map of p53 transcription-factor binding sites in the human genome. Cell 2006, 124:207-219.
42. Wu X., Wu J., Huang J., Powell W.C., Zhang J., Matusik R.J., Sangiorgi F.O., Maxson R.E., Sucov H.M., Roy-Burman P. Generation of a prostate epithelial cell-specific Cre transgenic mouse model for tissue-specific gene ablation. Mech. Dev. 2001, 101:61-69.
43. Wu L., Grigoryan A.V., Li Y., Hao B., Pagano M., Cardozo T.J. Specific small molecule inhibitors of Skp2-mediated p27 degradation. Chem. Biol. 2012, 19:1515-1524.
44. Xuan Z., Zhao F., Wang J., Chen G., Zhang M.Q. Genome-wide promoter extraction and analysis in human, mouse, and rat. Genome Biol. 2005, 6:R72.
45. Zhou Z., Flesken-Nikitin A., Corney D.C., Wang W., Goodrich D.W., Roy-Burman P., Nikitin A.Y. Synergy of p53 and Rb deficiency in a conditional mouse model for metastatic prostate cancer. Cancer Res. 2006, 66:7889-7898.
46. Zhu W., Chen Y., Dutta A. Rereplication by depletion of geminin is seen regardless of p53 status and activates a G2/M checkpoint. Mol. Cell. Biol. 2004, 24:7140-7150.