MDM2 Associates with Polycomb Repressor Complex 2 and Enhances Stemness-Promoting Chromatin Modifications Independent of p53

Molecular Cell

Volumn 61, Issue 1, 2016, Pages 68-83

  Wienken, Magdalena ^a   Dickmanns, Antje ^a   Nemajerova, Alice ^b   Kramer, Daniela ^a   Najafova, Zeynab ^a   Weiss, Miriam ^a   Karpiuk, Oleksandra ^a   Kassem, Moustapha ^c   Zhang, Yanping ^d   Lozano, Guillermina ^e   Johnsen, Steven A ^a   Moll, Ute M ^a,b   Zhang, Xin ^a   Dobbelstein, Matthias ^a  

^a UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^b STONY BROOK UNIVERSITY   (United States)

^c UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^d UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HISTONE H2A; HISTONE H3; LYSINE; POLYCOMB REPRESSIVE COMPLEX 2; PROTEIN MDM2; PROTEIN P53; TRANSCRIPTION FACTOR EZH2; BMI1 PROTEIN; HISTONE; MDM2 PROTEIN, HUMAN; MDM2 PROTEIN, MOUSE; RNF2 PROTEIN, HUMAN; RNF2 PROTEIN, MOUSE; TP53 PROTEIN, HUMAN; UBIQUITIN PROTEIN LIGASE;

ANIMAL CELL; ARTICLE; CANCER CELL; CELL DIFFERENTIATION; CELL FATE; CELL PROLIFERATION; CELL SURVIVAL; CHROMATIN; CONTROLLED STUDY; GENE REPRESSION; HISTONE METHYLATION; HISTONE UBIQUITINATION; MESENCHYMAL STEM CELL; MOUSE; NONHUMAN; PLURIPOTENT STEM CELL; ANIMAL; BONE DEVELOPMENT; CANCER STEM CELL; CELL LINEAGE; CHROMATIN ASSEMBLY AND DISASSEMBLY; GENE EXPRESSION REGULATION; GENETIC TRANSFECTION; GENETICS; HCT116 CELL LINE; HUMAN; INDUCED PLURIPOTENT STEM CELL; MCF 7 CELL LINE; MESENCHYMAL STROMA CELL; METABOLISM; METHYLATION; PHENOTYPE; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TIME FACTOR; UBIQUITINATION;

ANIMALS; CELL DIFFERENTIATION; CELL LINEAGE; CELL PROLIFERATION; CELL SURVIVAL; CHROMATIN ASSEMBLY AND DISASSEMBLY; GENE EXPRESSION REGULATION, NEOPLASTIC; HCT116 CELLS; HISTONES; HUMANS; INDUCED PLURIPOTENT STEM CELLS; MCF-7 CELLS; MESENCHYMAL STROMAL CELLS; METHYLATION; MICE; NEOPLASTIC STEM CELLS; OSTEOGENESIS; PHENOTYPE; POLYCOMB REPRESSIVE COMPLEX 1; POLYCOMB REPRESSIVE COMPLEX 2; PROTO-ONCOGENE PROTEINS C-MDM2; RNA INTERFERENCE; SIGNAL TRANSDUCTION; TIME FACTORS; TRANSFECTION; TUMOR SUPPRESSOR PROTEIN P53; UBIQUITIN-PROTEIN LIGASES; UBIQUITINATION;

EID: 84953635133     PISSN: 10972765     EISSN: 10974164     Source Type: Journal    
DOI: 10.1016/j.molcel.2015.12.008     Document Type: Article

References (82)

1. Abdel-Wahab O., Adli M., LaFave L.M., Gao J., Hricik T., Shih A.H., Pandey S., Patel J.P., Chung Y.R., Koche R., et al. ASXL1 mutations promote myeloid transformation through loss of PRC2-mediated gene repression. Cancer Cell 2012, 22:180-193.
2. Armstrong J.F., Kaufman M.H., Harrison D.J., Clarke A.R. High-frequency developmental abnormalities in p53-deficient mice. Curr. Biol. 1995, 5:931-936.
3. Ben-Saadon R., Zaaroor D., Ziv T., Ciechanover A. The polycomb protein Ring1B generates self atypical mixed ubiquitin chains required for its in vitro histone H2A ligase activity. Mol. Cell 2006, 24:701-711.
4. Bhatnagar S., Gazin C., Chamberlain L., Ou J., Zhu X., Tushir J.S., Virbasius C.M., Lin L., Zhu L.J., Wajapeyee N., Green M.R. TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein. Nature 2014, 516:116-120.
5. Blackledge N.P., Farcas A.M., Kondo T., King H.W., McGouran J.F., Hanssen L.L., Ito S., Cooper S., Kondo K., Koseki Y., et al. Variant PRC1 complex-dependent H2A ubiquitylation drives PRC2 recruitment and polycomb domain formation. Cell 2014, 157:1445-1459.
6. Bohlman S., Manfredi J.J. p53-independent effects of Mdm2. Subcell. Biochem. 2014, 85:235-246.
7. Bouska A., Eischen C.M. Murine double minute 2: p53-independent roads lead to genome instability or death. Trends Biochem. Sci. 2009, 34:279-286.
8. Boyer L.A., Plath K., Zeitlinger J., Brambrink T., Medeiros L.A., Lee T.I., Levine S.S., Wernig M., Tajonar A., Ray M.K., et al. Polycomb complexes repress developmental regulators in murine embryonic stem cells. Nature 2006, 441:349-353.
9. Brown D.R., Thomas C.A., Deb S.P. The human oncoprotein MDM2 arrests the cell cycle: elimination of its cell-cycle-inhibitory function induces tumorigenesis. EMBO J. 1998, 17:2513-2525.
10. Bunz F., Dutriaux A., Lengauer C., Waldman T., Zhou S., Brown J.P., Sedivy J.M., Kinzler K.W., Vogelstein B. Requirement for p53 and p21 to sustain G2 arrest after DNA damage. Science 1998, 282:1497-1501.
11. Cao R., Wang L., Wang H., Xia L., Erdjument-Bromage H., Tempst P., Jones R.S., Zhang Y. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 2002, 298:1039-1043.
12. Cooper S., Dienstbier M., Hassan R., Schermelleh L., Sharif J., Blackledge N.P., De Marco V., Elderkin S., Koseki H., Klose R., et al. Targeting polycomb to pericentric heterochromatin in embryonic stem cells reveals a role for H2AK119u1 in PRC2 recruitment. Cell Rep. 2014, 7:1456-1470.
13. Dobbelstein M., Moll U. Targeting tumour-supportive cellular machineries in anticancer drug development. Nat. Rev. Drug Discov. 2014, 13:179-196.
14. Dobbelstein M., Sørensen C.S. Exploiting replicative stress to treat cancer. Nat. Rev. Drug Discov. 2015, 14:405-423.
15. Dobbelstein M., Wienzek S., König C., Roth J. Inactivation of the p53-homologue p73 by the mdm2-oncoprotein. Oncogene 1999, 18:2101-2106.
16. Dohmesen C., Koeppel M., Dobbelstein M. Specific inhibition of Mdm2-mediated neddylation by Tip60. Cell Cycle 2008, 7:222-231.
17. Donehower L.A., Harvey M., Slagle B.L., McArthur M.J., Montgomery C.A., Butel J.S., Bradley A. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature 1992, 356:215-221.
18. Easwaran H., Tsai H.C., Baylin S.B. Cancer epigenetics: tumor heterogeneity, plasticity of stem-like states, and drug resistance. Mol. Cell 2014, 54:716-727.
19. Farcas A.M., Blackledge N.P., Sudbery I., Long H.K., McGouran J.F., Rose N.R., Lee S., Sims D., Cerase A., Sheahan T.W., et al. KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands. eLife 2012, 1:e00205.
20. Forslund A., Zeng Z., Qin L.X., Rosenberg S., Ndubuisi M., Pincas H., Gerald W., Notterman D.A., Barany F., Paty P.B. MDM2 gene amplification is correlated to tumor progression but not to the presence of SNP309 or TP53 mutational status in primary colorectal cancers. Mol. Cancer Res. 2008, 6:205-211.
21. Frum R.A., Singh S., Vaughan C., Mukhopadhyay N.D., Grossman S.R., Windle B., Deb S., Deb S.P. The human oncoprotein MDM2 induces replication stress eliciting early intra-S-phase checkpoint response and inhibition of DNA replication origin firing. Nucleic Acids Res. 2014, 42:926-940.
22. Fussbroich B., Wagener N., Macher-Goeppinger S., Benner A., Fälth M., Sültmann H., Holzer A., Hoppe-Seyler K., Hoppe-Seyler F. EZH2 depletion blocks the proliferation of colon cancer cells. PLoS ONE 2011, 6:e21651.
23. Gannon H.S., Woda B.A., Jones S.N. ATM phosphorylation of Mdm2 Ser394 regulates the amplitude and duration of the DNA damage response in mice. Cancer Cell 2012, 21:668-679.
24. Gao Z., Zhang J., Bonasio R., Strino F., Sawai A., Parisi F., Kluger Y., Reinberg D. PCGF homologs, CBX proteins, and RYBP define functionally distinct PRC1 family complexes. Mol. Cell 2012, 45:344-356.
25. Grossman S.R., Perez M., Kung A.L., Joseph M., Mansur C., Xiao Z.X., Kumar S., Howley P.M., Livingston D.M. p300/MDM2 complexes participate in MDM2-mediated p53 degradation. Mol. Cell 1998, 2:405-415.
26. Gupta P.B., Chaffer C.L., Weinberg R.A. Cancer stem cells: mirage or reality?. Nat. Med. 2009, 15:1010-1012.
27. Hansen K.H., Bracken A.P., Pasini D., Dietrich N., Gehani S.S., Monrad A., Rappsilber J., Lerdrup M., Helin K. A model for transmission of the H3K27me3 epigenetic mark. Nat. Cell Biol. 2008, 10:1291-1300.
28. He A., Shen X., Ma Q., Cao J., von Gise A., Zhou P., Wang G., Marquez V.E., Orkin S.H., Pu W.T. PRC2 directly methylates GATA4 and represses its transcriptional activity. Genes Dev. 2012, 26:37-42.
29. He J., Shen L., Wan M., Taranova O., Wu H., Zhang Y. Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes. Nat. Cell Biol. 2013, 15:373-384.
30. Ho L., Miller E.L., Ronan J.L., Ho W.Q., Jothi R., Crabtree G.R. esBAF facilitates pluripotency by conditioning the genome for LIF/STAT3 signalling and by regulating polycomb function. Nat. Cell Biol. 2011, 13:903-913.
31. Honda R., Yasuda H. Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase. Oncogene 2000, 19:1473-1476.
32. Honda R., Tanaka H., Yasuda H. Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 1997, 420:25-27.
33. Hu W., Feng Z., Teresky A.K., Levine A.J. p53 regulates maternal reproduction through LIF. Nature 2007, 450:721-724.
34. Hu H., Yang Y., Ji Q., Zhao W., Jiang B., Liu R., Yuan J., Liu Q., Li X., Zou Y., et al. CRL4B catalyzes H2AK119 monoubiquitination and coordinates with PRC2 to promote tumorigenesis. Cancer Cell 2012, 22:781-795.
35. Itahana K., Mao H., Jin A., Itahana Y., Clegg H.V., Lindström M.S., Bhat K.P., Godfrey V.L., Evan G.I., Zhang Y. Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation. Cancer Cell 2007, 12:355-366.
36. Jones S.N., Roe A.E., Donehower L.A., Bradley A. Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature 1995, 378:206-208.
37. Kalb R., Latwiel S., Baymaz H.I., Jansen P.W., Müller C.W., Vermeulen M., Müller J. Histone H2A monoubiquitination promotes histone H3 methylation in Polycomb repression. Nat. Struct. Mol. Biol. 2014, 21:569-571.
38. Kaneko S., Bonasio R., Saldaña-Meyer R., Yoshida T., Son J., Nishino K., Umezawa A., Reinberg D. Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin. Mol. Cell 2014, 53:290-300.
39. Knutson S.K., Warholic N.M., Wigle T.J., Klaus C.R., Allain C.J., Raimondi A., Porter Scott M., Chesworth R., Moyer M.P., Copeland R.A., et al. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc. Natl. Acad. Sci. USA 2013, 110:7922-7927.
40. Krizhanovsky V., Lowe S.W. Stem cells: The promises and perils of p53. Nature 2009, 460:1085-1086.
41. Lee D.F., Su J., Kim H.S., Chang B., Papatsenko D., Zhao R., Yuan Y., Gingold J., Xia W., Darr H., et al. Modeling familial cancer with induced pluripotent stem cells. Cell 2015, 161:240-254.
42. Legube G., Linares L.K., Lemercier C., Scheffner M., Khochbin S., Trouche D. Tip60 is targeted to proteasome-mediated degradation by Mdm2 and accumulates after UV irradiation. EMBO J. 2002, 21:1704-1712.
43. Li H., Collado M., Villasante A., Strati K., Ortega S., Cañamero M., Blasco M.A., Serrano M. The Ink4/Arf locus is a barrier for iPS cell reprogramming. Nature 2009, 460:1136-1139.
44. Margueron R., Reinberg D. The Polycomb complex PRC2 and its mark in life. Nature 2011, 469:343-349.
45. Marine J.C., Lozano G. Mdm2-mediated ubiquitylation: p53 and beyond. Cell Death Differ. 2010, 17:93-102.
46. Maya R., Balass M., Kim S.T., Shkedy D., Leal J.F., Shifman O., Moas M., Buschmann T., Ronai Z., Shiloh Y., et al. ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes Dev. 2001, 15:1067-1077.
47. McCabe M.T., Ott H.M., Ganji G., Korenchuk S., Thompson C., Van Aller G.S., Liu Y., Graves A.P., Della Pietra A., Diaz E., et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature 2012, 492:108-112.
48. Minsky N., Oren M. The RING domain of Mdm2 mediates histone ubiquitylation and transcriptional repression. Mol. Cell 2004, 16:631-639.
49. Mo P., Wang H., Lu H., Boyd D.D., Yan C. MDM2 mediates ubiquitination and degradation of activating transcription factor 3. J. Biol. Chem. 2010, 285:26908-26915.
50. Montes de Oca Luna R., Wagner D.S., Lozano G. Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 1995, 378:203-206.
51. Natsume A., Ito M., Katsushima K., Ohka F., Hatanaka A., Shinjo K., Sato S., Takahashi S., Ishikawa Y., Takeuchi I., et al. Chromatin regulator PRC2 is a key regulator of epigenetic plasticity in glioblastoma. Cancer Res. 2013, 73:4559-4570.
52. O'Carroll D., Erhardt S., Pagani M., Barton S.C., Surani M.A., Jenuwein T. The polycomb-group gene Ezh2 is required for early mouse development. Mol. Cell. Biol. 2001, 21:4330-4336.
53. Oliner J.D., Kinzler K.W., Meltzer P.S., George D.L., Vogelstein B. Amplification of a gene encoding a p53-associated protein in human sarcomas. Nature 1992, 358:80-83.
54. Olivier M., Hollstein M., Hainaut P. TP53 mutations in human cancers: origins, consequences, and clinical use. Cold Spring Harb. Perspect. Biol. 2010, 2:a001008.
55. Onder T.T., Kara N., Cherry A., Sinha A.U., Zhu N., Bernt K.M., Cahan P., Marcarci B.O., Unternaehrer J., Gupta P.B., et al. Chromatin-modifying enzymes as modulators of reprogramming. Nature 2012, 483:598-602.
56. Peng J.C., Valouev A., Swigut T., Zhang J., Zhao Y., Sidow A., Wysocka J. Jarid2/Jumonji coordinates control of PRC2 enzymatic activity and target gene occupancy in pluripotent cells. Cell 2009, 139:1290-1302.
57. Qin J.J., Wang W., Voruganti S., Wang H., Zhang W.D., Zhang R. Identification of a new class of natural product MDM2 inhibitor: In vitro and in vivo anti-breast cancer activities and target validation. Oncotarget 2015, 6:2623-2640.
58. Sah V.P., Attardi L.D., Mulligan G.J., Williams B.O., Bronson R.T., Jacks T. A subset of p53-deficient embryos exhibit exencephaly. Nat. Genet. 1995, 10:175-180.
59. Sanchez-Cespedes M., Reed A.L., Buta M., Wu L., Westra W.H., Herman J.G., Yang S.C., Jen J., Sidransky D. Inactivation of the INK4A/ARF locus frequently coexists with TP53 mutations in non-small cell lung cancer. Oncogene 1999, 18:5843-5849.
60. Shah N., Sukumar S. The Hox genes and their roles in oncogenesis. Nat. Rev. Cancer 2010, 10:361-371.
61. Sher F., Boddeke E., Olah M., Copray S. Dynamic changes in Ezh2 gene occupancy underlie its involvement in neural stem cell self-renewal and differentiation towards oligodendrocytes. PLoS ONE 2012, 7:e40399.
62. Sherr C.J. Tumor surveillance via the ARF-p53 pathway. Genes Dev. 1998, 12:2984-2991.
63. Shin Y.J., Kim J.-H. The role of EZH2 in the regulation of the activity of matrix metalloproteinases in prostate cancer cells. PLoS ONE 2012, 7:e30393.
64. Simon J.A., Kingston R.E. Occupying chromatin: Polycomb mechanisms for getting to genomic targets, stopping transcriptional traffic, and staying put. Mol. Cell 2013, 49:808-824.
65. Steffen P.A., Ringrose L. What are memories made of? How Polycomb and Trithorax proteins mediate epigenetic memory. Nat. Rev. Mol. Cell Biol. 2014, 15:340-356.
66. Stommel J.M., Wahl G.M. Accelerated MDM2 auto-degradation induced by DNA-damage kinases is required for p53 activation. EMBO J. 2004, 23:1547-1556.
67. Taherbhoy A.M., Huang O.W., Cochran A.G. BMI1-RING1B is an autoinhibited RING E3 ubiquitin ligase. Nat. Commun. 2015, 6:7621.
68. Takahashi K., Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006, 126:663-676.
69. Tavares L., Dimitrova E., Oxley D., Webster J., Poot R., Demmers J., Bezstarosti K., Taylor S., Ura H., Koide H., et al. RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3. Cell 2012, 148:664-678.
70. Twine N.A., Chen L., Pang C.N., Wilkins M.R., Kassem M. Identification of differentiation-stage specific markers that define the ex vivo osteoblastic phenotype. Bone 2014, 67:23-32.
71. Utikal J., Polo J.M., Stadtfeld M., Maherali N., Kulalert W., Walsh R.M., Khalil A., Rheinwald J.G., Hochedlinger K. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 2009, 460:1145-1148.
72. Varambally S., Cao Q., Mani R.S., Shankar S., Wang X., Ateeq B., Laxman B., Cao X., Jing X., Ramnarayanan K., et al. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 2008, 322:1695-1699.
73. Wade M., Li Y.C., Wahl G.M. MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat. Rev. Cancer 2013, 13:83-96.
74. Wang H., Wang L., Erdjument-Bromage H., Vidal M., Tempst P., Jones R.S., Zhang Y. Role of histone H2A ubiquitination in Polycomb silencing. Nature 2004, 431:873-878.
75. Wang L., Zeng X., Chen S., Ding L., Zhong J., Zhao J.C., Wang L., Sarver A., Koller A., Zhi J., et al. BRCA1 is a negative modulator of the PRC2 complex. EMBO J. 2013, 32:1584-1597.
76. Wang W., Qin J.J., Voruganti S., Srivenugopal K.S., Nag S., Patil S., Sharma H., Wang M.H., Wang H., Buolamwini J.K., Zhang R. The pyrido[b]indole MDM2 inhibitor SP-141 exerts potent therapeutic effects in breast cancer models. Nat. Commun. 2014, 5:5086.
77. Wang W., Qin J.J., Voruganti S., Wang M.H., Sharma H., Patil S., Zhou J., Wang H., Mukhopadhyay D., Buolamwini J.K., et al. Identification of a new class of MDM2 inhibitor that inhibits growth of orthotopic pancreatic tumors in mice. Gastroenterology 2014, 147:893-902.
78. Wei Y., Chen Y.H., Li L.Y., Lang J., Yeh S.P., Shi B., Yang C.C., Yang J.Y., Lin C.Y., Lai C.C., Hung M.C. CDK1-dependent phosphorylation of EZH2 suppresses methylation of H3K27 and promotes osteogenic differentiation of human mesenchymal stem cells. Nat. Cell Biol. 2011, 13:87-94.
79. Wu X., Johansen J.V., Helin K. Fbxl10/Kdm2b recruits polycomb repressive complex 1 to CpG islands and regulates H2A ubiquitylation. Mol. Cell 2013, 49:1134-1146.
80. Yang Y., Ludwig R.L., Jensen J.P., Pierre S.A., Medaglia M.V., Davydov I.V., Safiran Y.J., Oberoi P., Kenten J.H., Phillips A.C., et al. Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells. Cancer Cell 2005, 7:547-559.
81. Zhang Y., Xiong Y., Yarbrough W.G. ARF promotes MDM2 degradation and stabilizes p53: ARF-INK4a locus deletion impairs both the Rb and p53 tumor suppression pathways. Cell 1998, 92:725-734.
82. Zhang Z., Wang H., Li M., Rayburn E.R., Agrawal S., Zhang R. Stabilization of E2F1 protein by MDM2 through the E2F1 ubiquitination pathway. Oncogene 2005, 24:7238-7247.