Regulation of MDM2 Stability After DNA Damage

Journal of Cellular Physiology

Volumn 230, Issue 10, 2015, Pages 2318-2327

  Li, Jiaqi ^a   Kurokawa, Manabu ^a,b  

^a DARTMOUTH MEDICAL SCHOOL   (United States)

^b NORRIS COTTON CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PROTEASOME; PROTEIN MDM2; PROTEIN P53; UBIQUITIN; UBIQUITIN PROTEIN LIGASE E3;

ANIMAL CELL; ANIMAL EXPERIMENT; APOPTOSIS; ARTICLE; CARCINOGENESIS; CELL DEATH; CELL STRESS; CONTROLLED STUDY; DNA DAMAGE; EMBRYO; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN STABILITY; REGULATORY MECHANISM; TUMOR GROWTH; ANIMAL; CELL CYCLE; GENETICS; HUMAN; METABOLISM;

ANIMALS; CELL CYCLE; DNA DAMAGE; HUMANS; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN STABILITY; PROTO-ONCOGENE PROTEINS C-MDM2; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84932608260     PISSN: 00219541     EISSN: 10974652     Source Type: Journal    
DOI: 10.1002/jcp.24994     Document Type: Article

References (76)

1. Allende-Vega N, Dias S, Milne D, Meek D. 2005. Phosphorylation of the acidic domain of Mdm2 by protein kinaseCK2. Mol Cell Biochem 274:85-90.
2. Allende-Vega N, Sparks A, Lane DP, Saville MK. 2010. MdmX is a substrate for the deubiquitinating enzyme USP2a. Oncogene 29:432-441.
3. Ang XL, Harper JW. 2005. SCF-mediated protein degradation and cell cycle control. Oncogene 24:2860-2870.
4. Barak Y, Juven T, Haffner R, Oren M. 1993. Mdm2 expression is induced by wild type p53 activity. EMBO J 12:461-468.
5. Bensimon A, Aebersold R, Shiloh Y. 2011. Beyond ATM: The protein kinase landscape of the DNA damage response. FEBS Lett.
6. Bernardi R, Scaglioni PP, Bergmann S, Horn HF, Vousden KH, Pandolfi PP. 2004. PML regulates p53 stability by sequestering Mdm2 to the nucleolus. Nat Cell Biol 6:665-672.
7. Blattner C, Hay T, Meek DW, Lane DP. 2002. Hypophosphorylation of Mdm2 augments p53 stability. Mol Cell Biol 22:6170-6182.
8. Boehme K a, Kulikov R, Blattner C. 2008. P53 stabilization in response to DNA damage requires Akt/PKB and DNA-PK. Proc Natl Acad Sci USA 105:7785-7790.
9. Bozulic L, Surucu B, Hynx D, Hemmings BA. 2008. PKBα/Akt1 Acts Downstream of DNA-PK in the DNA Double-Strand Break Response and Promotes Survival. Mol Cell 30:203-213.
10. Buschmann T, Fuchs SY, Fuchs SY, Lee CG, Lee CG, Pan ZQ, Pan ZQ, Ronai Z, Ronai Z. 2000. SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53. Cell 101:753-762.
11. Buschmann T, Lerner D, Lee CG, Ronai Z. 2001. The Mdm-2 Amino Terminus Is Required for Mdm2 Binding and SUMO-1 Conjugation by the E2 SUMO-1 Conjugating Enzyme Ubc9. J Biol Chem 276:40389-40395.
12. Chen L, Gilkes DM, Pan Y, Lane WS, Chen J. 2005. ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage. EMBO J 24:3411-3422.
13. Cheng Q, Chen L, Li Z, Lane WS, Chen J. 2009. ATM activates p53 by regulating MDM2 oligomerization and E3 processivity. EMBO J 28:3857-3867.
14. Cheng Q, Cross B, Li B, Chen L, Li Z, Chen J. 2011. Regulation of MDM2 E3 Ligase Activity by Phosphorylation after DNA Damage. Mol Cell Biol.
15. Cummins JM, Vogelstein B. 2004. HAUSP is required for p53 destabilization. Cell Cycle.
16. Feng J, Tamaskovic R, Yang Z, Brazil DP, Merlo A, Hess D, Hemmings BA. 2004. Stabilization of Mdm2 via decreased ubiquitination is mediated by protein kinase B/Akt-dependent phosphorylation. J Biol Chem 279:35510-35517.
17. Gannon HS, Woda BA, Jones SN. 2012. ATM Phosphorylation of Mdm2 Ser394 Regulates the Amplitude and Duration of the DNA Damage Response in Mice. Cancer Cell 21:668-679.
18. Ghosh M, Weghorst K, Berberich SJ. 2005. MdmX inhibits ARF mediated Mdm2 sumoylation. Cell Cycle 4:604-608.
19. Grier JD, Xiong S, Elizondo-Fraire AC, Parant JM, Lozano G. 2006. Tissue-specific differences of p53 inhibition by Mdm2 and Mdm4. Mol Cell Biol 26:192-198.
20. Gu J, Kawai H, Nie L, Kitao H, Wiederschain D, Jochemsen AG, Parant J, Lozano G, Yuan ZM. 2002. Mutual dependence of MDM2 and MDMX in their functional inactivation of p53. J Biol Chem 277:19251-19254.
21. Haupt Y, Maya R, Kazaz A, Oren M. 1997. Mdm2 promotes the rapid degradation of p53. Nature 387:296-299.
22. He Y, Tollini L, Kim TH, Itahana Y, Zhang Y. 2014. The anaphase-promoting complex/cyclosome is an E3 ubiquitin ligase for Mdm2. Cell Cycle 13:2101-2109.
23. Honda R, Yasuda H. 1999. Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53. EMBO J 18:22-27.
24. Inuzuka H, Tseng A, Gao D, Zhai B, Zhang Q, Shaik S, Wan L, Ang XL, Mock C, Yin H, Stommel JM, Gygi S, Lahav G, Asara J, Xiao Z-XJ, Kaelin WG, Harper JW, Wei W. 2010. Phosphorylation by casein kinase I promotes the turnover of the Mdm2 oncoprotein via the SCF(beta-TRCP) ubiquitin ligase. Cancer Cell 18:147-159.
25. Itahana K, Mao H, Jin A, Itahana Y, Clegg HV, Lindström MS, Bhat KP, Godfrey VL, Evan GI, Zhang Y. 2007. Targeted inactivation of Mdm2 RING finger E3 ubiquitin ligase activity in the mouse reveals mechanistic insights into p53 regulation. Cancer Cell 12:355-366.
26. Jain AK, Barton MC. 2010. Making sense of ubiquitin ligases that regulate p53. Cancer Biol Ther.
27. Jin Y, Dai M-S, Lu SZ, Xu Y, Luo Z, Zhao Y, Lu H. 2006. 14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation. EMBO J 25:1207-1218.
28. Jin Y, Zeng SX, Lee H, Lu H. 2004. MDM2 Mediates p300/CREB-binding Protein-associated Factor Ubiquitination and Degradation. J Biol Chem 279:20035-20043.
29. Jones SN, Roe AE, Donehower LA, Bradley A. 1995. Rescue of embryonic lethality in Mdm2-deficient mice by absence of p53. Nature 378:206-208.
30. Kawai H, Lopez-Pajares V, Kim MM, Wiederschain D, Yuan ZM. 2007. RING domain-mediated interaction is a requirement for MDM2's E3 ligase activity. Cancer Res 67:6026-6030.
31. Kostic M, Matt T, Martinez-Yamout MA, Dyson HJ, Wright PE. 2006. Solution Structure of the Hdm2 C2H2C4 RING, a Domain Critical for Ubiquitination of p53. J Mol Biol 363:433-450.
32. Kulikov R, Boehme KA, Blattner C. 2005. Glycogen synthase kinase 3-dependent phosphorylation of Mdm2 regulates p53 abundanc. Mol Cell Biol 25:7170-7180.
33. Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, Pavletich NP. 1996. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274:948-953.
34. Lane DP. 1992. Cancer. p53, guardian of the genome. Nature 358:15-16.
35. Li M, Brooks CL, Kon N, Gu W. 2004. A dynamic role of HAUSP in the p53-Mdm2 pathway. Mol Cell 13:879-886.
36. Li M, Chen D, Shiloh A, Luo J, Nikolaev AY, Qin J, Gu W. 2002. Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature 416:648-653.
37. Linares LK, Kiernan R, Triboulet R, Chable-Bessia C, Latreille D, Cuvier O, Lacroix M, Le Cam L, Coux O, Benkirane M. 2007. Intrinsic ubiquitination activity of PCAF controls the stability of the oncoprotein Hdm2. Nat Cell Biol 9:331-338.
38. Linke K, Mace PD, Smith CA, Vaux DL, Silke J, Day CL. 2008. Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans. Cell Death Differ 15:841-848.
39. Long J, Parkin B, Ouillette P, Bixby D, Shedden K, Erba H, Wang S, Malek SN. 2010. Multiple distinct molecular mechanisms influence sensitivity and resistance to MDM2 inhibitors in adult acute myelogenous leukemia. Blood 116:71-80.
40. Lopez-Pajares V, Kim MM, Yuan ZM. 2008. Phosphorylation of MDMX mediated by Akt leads to stabilization and induces 14- 3- 3 binding. J Biol Chem 283:13707-13713.
41. Lu X, Ma O, Nguyen TA, Jones SN, Oren M, Donehower LA. 2007. The Wip1 Phosphatase Acts as a Gatekeeper in the p53-Mdm2 Autoregulatory Loop. Cancer Cell 12:342-354.
42. Maya R, Balass M, Kim ST, Shkedy D, Martinez Leal JF, Shifman O, Moas M, Buschmann T, Ronai Z, Shiloh Y, Kastan MB, Katzir E, Oren M. 2001. ATM-dependent phosphorylation of Mdm2 on serine 395: Role in p53 activation by DNA damage. Genes Dev 15:1067-1077.
43. Mayo LD, Turchi JJ, Berberich SJ. 1997. Mdm-2 phosphorylation by DNA-dependent protein kinase prevents interaction with p53. Cancer Res 57:5013-5016.
44. Meulmeester E, Pereg Y, Shiloh Y, Jochemsen AG. 2005. ATM-mediated phosphorylations inhibit Mdmx/Mdm2 stabilization by HAUSP in favor of p53 activation. Cell Cycle 4:1166-1170.
45. Migliorini D, Danovi D, Colombo E, Carbone R, Pelicci PG, Marine JC. 2002. Hdmx recruitment into the nucleus by Hdm2 is essential for its ability to regulate p53 stability and transactivation. J Biol Chem 277:7318-7323.
46. Montes de Oca Luna R, Wagner DS, Lozano G. 1995. Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 378:203-206.
47. Pan Y, Chen J. 2003. MDM2 promotes ubiquitination and degradation of MDMX. Mol Cell Biol 23:5113-5121.
48. Pant V, Xiong S, Iwakuma T, Quintás-Cardama A, Lozano G. 2011. Heterodimerization of Mdm2 and Mdm4 is critical for regulating p53 activity during embryogenesis but dispensable for p53 and Mdm2 stability. Proc Natl Acad Sci USA 108:11995-12000.
49. Parant J, Chavez-Reyes A, Little NA, Yan W, Reinke V, Jochemsen AG, Lozano G. 2001. Rescue of embryonic lethality in Mdm4-null mice by loss of Trp53 suggests a nonoverlapping pathway with MDM2 to regulate p53. Nat Genet 29:92-95.
50. Priest C, Prives C, Poyurovsky MV. 2010. Deconstructing nucleotide binding activity of the Mdm2 RING domain. Nucleic Acids Res 38:7587-7598.
51. Riley MF, Lozano G. 2012. The Many Faces of MDM2 Binding Partners. Genes Cancer 3:226-239.
52. Sharp DA, Kratowicz SA, Sank MJ, George DL. 1999. Stabilization of the MDM2 oncoprotein by interaction with the structurally related MDMX protein. J Biol Chem 274:38189-38196.
53. Shinozaki T, Nota A, Taya Y, Okamoto K. 2003. Functional role of Mdm2 phosphorylation by ATR in attenuation of p53 nuclear export. Oncogene 22:8870-8880.
54. Stevenson LF, Sparks A, Allende-Vega N, Xirodimas DP, Lane DP, Saville MK. 2007. The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting Mdm2. EMBO J 26:976-986.
55. Stommel JM, Wahl GM. 2004. Accelerated MDM2 auto-degradation induced by DNA-damage kinases is required for p53 activation. EMBO J 23:1547-1556.
56. Tang J, Agrawal T, Cheng Q, Qu L, Brewer MD, Chen J, Yang X. 2013. Phosphorylation of Daxx by ATM Contributes to DNA Damage-Induced p53 Activation. PLoS ONE 8.
57. Tang J, Qu L-K, Zhang J, Wang W, Michaelson JS, Degenhardt YY, El-Deiry WS, Yang X. 2006. Critical role for Daxx in regulating Mdm2. Nat Cell Biol 8:855-862.
58. Tanimura S, Ohtsuka S, Mitsui K, Shirouzu K, Yoshimura A, Ohtsubo M. 1999. MDM2 interacts with MDMX through their RING finger domains. FEBS Lett 447:5-9.
59. Tao W, Levine AJ. 1999. P19(ARF) stabilizes p53 by blocking nucleo-cytoplasmic shuttling of Mdm2. Proc Natl Acad Sci USA 96:6937-6941.
60. Tollini L a, Jin A, Park J, Zhang Y. 2014. Regulation of p53 by Mdm2 E3 ligase function is dispensable in embryogenesis and development, but essential in response to DNA damage. Cancer Cell 26:235-247.
61. Tovar C, Rosinski J, Filipovic Z, Higgins B, Kolinsky K, Hilton H, Zhao X, Vu BT, Qing W, Packman K, Myklebost O, Heimbrook DC, Vassilev LT. 2006. Small-molecule MDM2 antagonists reveal aberrant p53 signaling in cancer: Implications for therapy. Proc Natl Acad Sci USA 103:1888-1893.
62. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, Kong N, Kammlott U, Lukacs C, Klein C, Fotouhi N, Liu EA. 2004. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303:844-848.
63. Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, Newman J, Reczek EE, Weissleder R, Jacks T. 2007. Restoration of p53 function leads to tumour regression in vivo. Nature 445:661-665.
64. Vousden KH, Prives C. 2009. Blinded by the Light: The Growing Complexity of p53. Cell 137:413-431.
65. Wang S, Guo M, Ouyang H, Li X, Cordon-Cardo C, Kurimasa A, Chen DJ, Fuks Z, Ling CC, Li GC. 2000. The catalytic subunit of DNA-dependent protein kinase selectively regulates p53-dependent apoptosis but not cell-cycle arrest. Proc Natl Acad Sci USA 97:1584-1588.
66. Wang YV, Leblanc M, Wade M, Jochemsen AG, Wahl GM. 2009. Increased Radioresistance and Accelerated B Cell Lymphomas in Mice with Mdmx Mutations that Prevent Modifications by DNA-Damage-Activated Kinases. Cancer Cell 16:33-43.
67. Wang Z, Inuzuka H, Zhong J, Fukushima H, Wan L, Liu P, Wei W. 2012. DNA damage-induced activation of ATM promotes beta-TRCP-mediated Mdm2 ubiquitination and destruction. Oncotarget 3:1026-1035. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22976441.
68. Waning DL, Lehman JA, Batuello CN, Mayo LD. 2011. C-Abl phosphorylation of Mdm2 facilitates Mdm2-Mdmx complex formation. J Biol Chem 286:216-222.
69. Watson IR, Li BK, Roche O, Blanch A, Ohh M, Irwin MS. 2010. Chemotherapy induces NEDP1-mediated destabilization of MDM2. Oncogene 29:297-304.
70. Weber JD, Taylor LJ, Roussel MF, Sherr CJ, Bar-Sagi D. 1999. Nucleolar Arf sequesters Mdm2 and activates p53. Nat Cell Biol 1:20-26.
71. Xirodimas DP, Chisholm J, Desterro JMS, Lane DP, Hay RT. 2002. P14ARF promotes accumulation of SUMO-1 conjugated (H) Mdm2. FEBS Lett 528:207-211.
72. Xu C, Fan CD, Wang X. 2015. Regulation of Mdm2 protein stability and the p53 response by NEDD 4-1 E3 ligase. Oncogene 34:281-289.
73. Yu GW, Rudiger S, Veprintsev D, Freund S, Fernandez-Fernandez MR, Fersht AR. 2006. The central region of HDM2 provides a second binding site for p53. Proc Natl Acad Sci USA 103:1227-1232.
74. Zhang X, Lin H, Guo H, Yang J, Jones SN, Jochemsen A, Lu X. 2009. Phosphorylation and degradation of MdmX is inhibited by Wip1 phosphatase in the DNA damage response. Cancer Res 69:7960-7968.
75. Zhou BP, Liao Y, Xia W, Zou Y, Spohn B, Hung MC. 2001. HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat Cell Biol 3:973-982.
76. Zou Q, Jin J, Hu H, Li HS, Romano S, Xiao Y, Nakaya M, Zhou X, Cheng X, Yang P, Lozano G, Zhu C, Watowich SS, Ullrich SE, Sun S-C. 2014. USP15 stabilizes MDM2 to mediate cancer-cell survival and inhibit antitumor T cell responses. Nat Immunol 15:562-570.