Mechanism of p53 stabilization by ATM after DNA damage

Cell Cycle

Volumn 9, Issue 3, 2010, Pages 472-478

  Cheng, Qian ^a   Chen, Jiandong ^a  

^a H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

Author keywords

ATM; MDM2; MDMX; Oligomerization; p53; Phosphorylation; Ubiquitination

Indexed keywords

ATM PROTEIN; DNA; LIGASE; PROTEIN MDM2; PROTEIN P53; CELL CYCLE PROTEIN; DNA BINDING PROTEIN; PROTEIN SERINE THREONINE KINASE; TUMOR SUPPRESSOR PROTEIN; UBIQUITIN PROTEIN LIGASE;

DNA DAMAGE; ENZYME ACTIVATION; ENZYME REGULATION; IONIZING RADIATION; OLIGOMERIZATION; PROTEIN MODIFICATION; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; REVIEW; UBIQUITINATION; AMINO ACID SEQUENCE; ANIMAL; ARTICLE; BIOLOGICAL MODEL; CHEMISTRY; METABOLISM; MOLECULAR GENETICS; MOUSE; PHOSPHORYLATION; PROTEIN QUATERNARY STRUCTURE;

AMINO ACID SEQUENCE; ANIMALS; CELL CYCLE PROTEINS; DNA DAMAGE; DNA-BINDING PROTEINS; MICE; MODELS, BIOLOGICAL; MOLECULAR SEQUENCE DATA; PHOSPHORYLATION; PROTEIN STABILITY; PROTEIN STRUCTURE, QUATERNARY; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS C-MDM2; TUMOR SUPPRESSOR PROTEIN P53; TUMOR SUPPRESSOR PROTEINS; UBIQUITIN-PROTEIN LIGASES; UBIQUITINATION;

EID: 77951935474     PISSN: 15384101     EISSN: 15514005     Source Type: Journal    
DOI: 10.4161/cc.9.3.10556     Document Type: Review

References (86)

1. Vousden KH, Lane DP. p53 in health and disease. Nat Rev Mol Cell Biol 2007; 8:275-83.
2. Leng RP, Lin Y, Ma W, Wu H, Lemmers B, Chung S, et al. Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell 2003; 112:779-91. (Pubitemid 36378882)
3. Dornan D, Wertz I, Shimizu H, Arnott D, Frantz GD, Dowd P, et al. The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature 2004; 429:86-92.
4. Montes de Oca Luna R, Wagner DS, Lozano G. Rescue of early embryonic lethality in mdm2-deficient mice by deletion of p53. Nature 1995; 378:203-6.
5. Grier JD, Xiong S, Elizondo-Fraire AC, Parant JM, Lozano G. Tissue-specific differences of p53 inhibition by Mdm2 and Mdm4. Mol Cell Biol 2006; 26:192-8. (Pubitemid 43753483)
6. Vassilev LT, Vu BT, Graves B, Carvajal D, Podlaski F, Filipovic Z, et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 2004; 303:844-8.
7. Shvarts A, Steegenga WT, Riteco N, van Laar T, Dekker P, Bazuine M, et al. MDMX: a novel p53-binding protein with some functional properties of MDM2. EMBO J 1996; 15:5349-57. (Pubitemid 26336217)
8. Finch RA, Donoviel DB, Potter D, Shi M, Fan A, Freed DD, et al. mdmx is a negative regulator of p53 activity in vivo. Cancer Res 2002; 62:3221-5. (Pubitemid 34602417)
9. Migliorini D, Lazzerini Denchi E, Danovi D, Jochemsen A, Capillo M, Gobbi A, et al. Mdm4 (Mdmx) regulates p53-induced growth arrest and neuronal cell death during early embryonic mouse development. Mol Cell Biol 2002; 22:5527-38. (Pubitemid 34755762)
10. Parant JM, Reinke V, Mims B, Lozano G. Organization, expression and localization of the murine mdmx gene and pseudogene. Gene 2001; 270:277-83. (Pubitemid 32525825)
11. Xiong S, Van Pelt CS, Elizondo-Fraire AC, Liu G, Lozano G. Synergistic roles of Mdm2 and Mdm4 for p53 inhibition in central nervous system development. Proc Natl Acad Sci USA 2006; 103:3226-31. (Pubitemid 43346452)
12. Maetens M, Doumont G, Clercq SD, Francoz S, Froment P, Bellefroid E, et al. Distinct roles of Mdm2 and Mdm4 in red cell production. Blood 2007; 109:2630-3. (Pubitemid 46425913)
13. Badciong JC, Haas AL. MdmX is a RING finger ubiquitin ligase capable of synergistically enhancing Mdm2 ubiquitination. J Biol Chem 2002; 277:49668-75.
14. Linares LK, Hengstermann A, Ciechanover A, Muller S, Scheffner M. HdmX stimulates Hdm2-mediated ubiquitination and degradation of p53. Proc Natl Acad Sci USA 2003; 100:12009-14. (Pubitemid 37271506)
15. Gu J, Kawai H, Nie L, Kitao H, Wiederschain D, Jochemsen AG, et al. Mutual dependence of MDM2 and MDMX in their functional inactivation of p53. J Biol Chem 2002; 277:19251-4. (Pubitemid 34967428)
16. Gilkes DM, Chen L, Chen J. MDMX regulation of p53 response to ribosomal stress. EMBO J 2006; 25:5614-25. (Pubitemid 44847201)
17. Toledo F, Krummel KA, Lee CJ, Liu CW, Rodewald LW, Tang M, et al. A mouse p53 mutant lacking the proline-rich domain rescues Mdm4 deficiency and provides insight into the Mdm2-Mdm4-p53 regulatory network. Cancer Cell 2006; 9:273-85.
18. Francoz S, Froment P, Bogaerts S, De Clercq S, Maetens M, Doumont G, et al. Mdm4 and Mdm2 cooperate to inhibit p53 activity in proliferating and quiescent cells in vivo. Proc Natl Acad Sci USA 2006; 103:3232-7. (Pubitemid 43346453)
19. Sdek P, Ying H, Chang DL, Qiu W, Zheng H, Touitou R, et al. MDM2 promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma protein. Mol Cell 2005; 20:699-708. (Pubitemid 41740692)
20. Kawai H, Wiederschain D, Yuan ZM. Critical contribution of the MDM2 acidic domain to p53 ubiquitination. Mol Cell Biol 2003; 23:4939-47. (Pubitemid 36793339)
21. Meulmeester E, Frenk R, Stad R, de Graaf P, Marine JC, Vousden KH, et al. Critical role for a central part of Mdm2 in the ubiquitylation of p53. Mol Cell Biol 2003; 23:4929-38. (Pubitemid 36793338)
22. Wang C, Ivanov A, Chen L, Fredericks WJ, Seto E, Rauscher FJ, 3rd, et al. MDM2 interaction with nuclear corepressor KAP1 contributes to p53 inactivation. EMBO J 2005; 24:3279-90. (Pubitemid 41348702)
23. Sui G, Affar el B, Shi Y, Brignone C, Wall NR, Yin P, et al. Yin Yang 1 is a negative regulator of p53. Cell 2004; 117:859-72.
24. Hu M, Gu L, Li M, Jeffrey PD, Gu W, Shi Y. Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7: implications for the regulation of the p53-MDM2 pathway. PLoS Biol 2006; 4:27. (Pubitemid 43275853)
25. Zhang Y, Wolf GW, Bhat K, Jin A, Allio T, Burkhart WA, et al. Ribosomal protein L11 negatively regulates oncoprotein MDM2 and mediates a p53-dependent ribosomal-stress checkpoint pathway. Mol Cell Biol 2003; 23:8902-12. (Pubitemid 37433388)
26. ARF peptide blocks Mdm2-dependent ubiquitination in vitro and can activate p53 in vivo. Oncogene 2000; 19:2312-23.
27. Sherr CJ. Divorcing ARF and p53: an unsettled case. Nat Rev Cancer 2006; 6:663-73.
28. Bhat KP, Itahana K, Jin A, Zhang Y. Essential role of ribosomal protein L11 in mediating growth inhibition-induced p53 activation. EMBO J 2004; 23:2402-12. (Pubitemid 38954847)
29. Lohrum MA, Ludwig RL, Kubbutat MH, Hanlon M, Vousden KH. Regulation of HDM2 activity by the ribosomal protein L11. Cancer Cell 2003; 3:577-87. (Pubitemid 36808652)
30. Dai MS, Lu H. Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5. J Biol Chem 2004; 279:44475-82. (Pubitemid 39430853)
31. Dai MS, Zeng SX, Jin Y, Sun XX, David L, Lu H. Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition. Mol Cell Biol 2004; 24:7654-68. (Pubitemid 39121491)
32. Kastan MB, Zhan Q, el-Deiry WS, Carrier F, Jacks T, Walsh WV, et al. A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell 1992; 71:587-97.
33. Shiloh Y. ATM and related protein kinases: safe-guarding genome integrity. Nat Rev Cancer 2003; 3:155-68.
34. Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 1998; 281:1674-7.
35. Shieh SY, Ikeda M, Taya Y, Prives C. DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 1997; 91:325-34.
36. Chehab NH, Malikzay A, Appel M, Halazonetis TD. Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Genes Dev 2000; 14:278-88.
37. Shieh SY, Ahn J, Tamai K, Taya Y, Prives C. The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev 2000; 14:289-300.
38. Bottger V, Bottger A, Garcia-Echeverria C, Ramos YF, van der Eb AJ, Jochemsen AG, et al. Comparative study of the p53-mdm2 and p53-MDMX interfaces. Oncogene 1999; 18:189-99.
39. Ashcroft M, Kubbutat MH, Vousden KH. Regulation of p53 function and stability by phosphorylation. Mol Cell Biol 1999; 19:1751-8.
40. Blattner C, Tobiasch E, Litfen M, Rahmsdorf HJ, Herrlich P. DNA damage induced p53 stabilization: no indication for an involvement of p53 phosphorylation. Oncogene 1999; 18:1723-32.
41. Dumaz N, Meek DW. Serine15 phosphorylation stimulates p53 transactivation but does not directly influence interaction with HDM2. EMBO J 1999; 18:7002-10.
42. Chao C, Herr D, Chun J, Xu Y. Ser18 and 23 phosphorylation is required for p53-dependent apoptosis and tumor suppression. EMBO J 2006; 25:2615-22.
43. MacPherson D, Kim J, Kim T, Rhee BK, Van Oostrom CT, DiTullio RA, et al. Defective apoptosis and B-cell lymphomas in mice with p53 point mutation at Ser 23. EMBO J 2004; 23:3689-99.
44. Chao C, Hergenhahn M, Kaeser MD, Wu Z, Saito S, Iggo R, et al. Cell type- and promoter-specific roles of Ser18 phosphorylation in regulating p53 responses. J Biol Chem 2003; 278:41028-33.
45. de Graaf P, Little NA, Ramos YF, Meulmeester E, Letteboer SJ, Jochemsen AG. Hdmx protein stability is regulated by the ubiquitin ligase activity of Mdm2. J Biol Chem 2003; 278:38315-24.
46. Kawai H, Wiederschain D, Kitao H, Stuart J, Tsai KK, Yuan ZM. DNA damage-induced MDMX degradation is mediated by MDM2. J Biol Chem 2003; 278:45946-53.
47. Pan Y, Chen J. MDM2 promotes ubiquitination and degradation of MDMX. Mol Cell Biol 2003; 23:5113-21.
48. Gilkes DM, Chen J. Distinct roles of MDMX in the regulation of p53 response to ribosomal stress. Cell Cycle 2007; 6:151-5.
49. Chen L, Gilkes DM, Pan Y, Lane WS, Chen J. ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage. EMBO J 2005; 24:3411-22.
50. Pereg Y, Shkedy D, de Graaf P, Meulmeester E, Edelson-Averbukh M, Salek M, et al. Phosphorylation of Hdmx mediates its Hdm2- and ATM-dependent degradation in response to DNA damage. Proc Natl Acad Sci USA 2005; 102:5056-61. (Pubitemid 40503738)
51. LeBron C, Chen L, Gilkes DM, Chen J. Regulation of MDMX nuclear import and degradation by Chk2 and 14-3-3. EMBO J 2006; 25:1196-206.
52. Pereg Y, Lam S, Teunisse A, Biton S, Meulmeester E, Mittelman L, et al. Differential roles of ATM-and Chk2-mediated phosphorylations of Hdmx in response to DNA damage. Mol Cell Biol 2006; 26:6819-31. (Pubitemid 44387632)
53. Meulmeester E, Maurice MM, Boutell C, Teunisse AF, Ovaa H, Abraham TE, et al. Loss of HAUSP-mediated deubiquitination contributes to DNA damage-induced destabilization of Hdmx and Hdm2. Mol Cell 2005; 18:565-76. (Pubitemid 40726233)
54. Meulmeester E, Pereg Y, Shiloh Y, Jochemsen AG. ATM-mediated phosphorylations inhibit Mdmx/ Mdm2 stabilization by HAUSP in favor of p53 activation. Cell Cycle 2005; 4:1166-70. (Pubitemid 41365384)
55. Wang YV, Leblanc M, Wade M, Jochemsen AG, Wahl GM. Increased radioresistance and accelerated B cell lymphomas in mice with Mdmx mutations that prevent modifications by DNA-damage-activated kinases. Cancer Cell 2009; 16:33-43.
56. Maya R, Balass M, Kim ST, Shkedy D, Leal JF, Shifman O, et al. ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes Dev 2001; 15:1067-77. (Pubitemid 32417300)
57. Shinozaki T, Nota A, Taya Y, Okamoto K. Functional role of Mdm2 phosphorylation by ATR in attenuation of p53 nuclear export. Oncogene 2003; 22:8870-80. (Pubitemid 38021503)
58. Sionov RV, Coen S, Goldberg Z, Berger M, Bercovich B, Ben-Neriah Y, et al. c-Abl regulates p53 levels under normal and stress conditions by preventing its nuclear export and ubiquitination. Mol Cell Biol 2001; 21:5869-78. (Pubitemid 32737804)
59. Goldberg Z, Vogt Sionov R, Berger M, Zwang Y, Perets R, Van Etten RA, et al. Tyrosine phosphorylation of Mdm2 by c-Abl: implications for p53 regulation. EMBO J 2002; 21:3715-27. (Pubitemid 34787045)
60. Lu X, Ma O, Nguyen TA, Jones SN, Oren M, Donehower LA. The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop. Cancer Cell 2007; 12:342-54. (Pubitemid 47539308)
61. Blattner C, Hay T, Meek DW, Lane DP. Hypophosphorylation of Mdm2 augments p53 stability. Mol Cell Biol 2002; 22:6170-82. (Pubitemid 34857837)
62. Kulikov R, Boehme KA, Blattner C. Glycogen synthase kinase 3-dependent phosphorylation of Mdm2 regulates p53 abundance. Mol Cell Biol 2005; 25:7170-80. (Pubitemid 41105913)
63. Tang J, Qu LK, Zhang J, Wang W, Michaelson JS, Degenhardt YY, et al. Critical role for Daxx in regulating Mdm2. Nat Cell Biol 2006; 8:855-62. (Pubitemid 44151589)
64. Stommel JM, Wahl GM. Accelerated MDM2 autodegradation induced by DNA-damage kinases is required for p53 activation. EMBO J 2004; 23:1547-56.
65. de Toledo SM, Azzam EI, Dahlberg WK, Gooding TB, Little JB. ATM complexes with HDM2 and promotes its rapid phosphorylation in a p53-independent manner in normal and tumor human cells exposed to ionizing radiation. Oncogene 2000; 19:6185-93.
66. Cheng Q, Chen L, Li Z, Lane WS, Chen J. ATM activates p53 by regulating MDM2 oligomerization and E3 processivity. EMBO J 2009.
67. Thrower JS, Hoffman L, Rechsteiner M, Pickart CM. Recognition of the polyubiquitin proteolytic signal. EMBO J 2000; 19:94-102.
68. Maki CG, Howley PM. Ubiquitination of p53 and p21 is differentially affected by ionizing and UV radiation. Mol Cell Biol 1997; 17:355-63.
69. Tang X, Orlicky S, Lin Z, Willems A, Neculai D, Ceccarelli D, et al. Suprafacial orientation of the SCFCdc4 dimer accommodates multiple geometries for substrate ubiquitination. Cell 2007; 129:1165-76. (Pubitemid 46891040)
70. Poyurovsky MV, Priest C, Kentsis A, Borden KL, Pan ZQ, Pavletich N, et al. The Mdm2 RING domain C-terminus is required for supramolecular assembly and ubiquitin ligase activity. EMBO J 2007; 26:90-101. (Pubitemid 46094702)
71. Linke K, Mace PD, Smith CA, Vaux DL, Silke J, Day CL. Structure of the MDM2/MDMX RING domain heterodimer reveals dimerization is required for their ubiquitylation in trans. Cell Death Differ 2008; 15:841-8. (Pubitemid 351524426)
72. Brzovic PS, Rajagopal P, Hoyt DW, King MC, Klevit RE. Structure of a BRCA1-BARD1 heterodimeric RING-RING complex. Nat Struct Biol 2001; 8:833-7. (Pubitemid 32923599)
73. Wu G, Xu G, Schulman BA, Jeffrey PD, Harper JW, Pavletich NP. Structure of a beta-TrCP1-Skp1- beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase. Mol Cell 2003; 11:1445-56. (Pubitemid 36776532)
74. Zheng N, Wang P, Jeffrey PD, Pavletich NP. Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases. Cell 2000; 102:533-9.
75. Passmore LA, Barford D. Getting into position: the catalytic mechanisms of protein ubiquitylation. Biochem J 2004; 379:513-25. (Pubitemid 38703635)
76. Breyer WA, Matthews BW. A structural basis for processivity. Protein Sci 2001; 10:1699-711.
77. Brzovic PS, Lissounov A, Christensen DE, Hoyt DW, Klevit RE. A UbcH5/ubiquitin noncovalent complex is required for processive BRCA1-directed ubiquitination. Mol Cell 2006; 21:873-80. (Pubitemid 43376136)
78. Saville MK, Sparks A, Xirodimas DP, Wardrop J, Stevenson LF, Bourdon JC, et al. Regulation of p53 by the ubiquitin-conjugating enzymes UbcH5B/C in vivo. J Biol Chem 2004; 279:42169-81. (Pubitemid 39313666)
79. Li M, Brooks CL, Wu-Baer F, Chen D, Baer R, Gu W. Mono- versus polyubiquitination: differential control of p53 fate by Mdm2. Science 2003; 302:1972-5. (Pubitemid 37523506)
80. Li W, Tu D, Li L, Wollert T, Ghirlando R, Brunger AT, et al. Mechanistic insights into active site-associated polyubiquitination by the ubiquitin-conjugating enzyme Ube2g2. Proc Natl Acad Sci USA 2009; 106:3722-7.
81. Li W, Tu D, Brunger AT, Ye Y. A ubiquitin ligase transfers preformed polyubiquitin chains from a conjugating enzyme to a substrate. Nature 2007; 446:333-7. (Pubitemid 46426147)
82. Ozkan E, Yu H, Deisenhofer J. Mechanistic insight into the allosteric activation of a ubiquitin-conjugating enzyme by RING-type ubiquitin ligases. Proc Natl Acad Sci USA 2005; 102:18890-5. (Pubitemid 43049537)
83. Shi D, Pop MS, Kulikov R, Love IM, Kung AL, Grossman SR. CBP and p300 are cytoplasmic E4 polyubiquitin ligases for p53. Proc Natl Acad Sci USA 2009; 106:16275-80.
84. Deshaies RJ, Joazeiro CA. RING domain E3 ubiquitin ligases. Annu Rev Biochem 2009; 78:399-434.
85. Barbash O, Zamfirova P, Lin DI, Chen X, Yang K, Nakagawa H, et al. Mutations in Fbx4 inhibit dimerization of the SCF(Fbx4) ligase and contribute to cyclin D1 overexpression in human cancer. Cancer Cell 2008; 14:68-78. (Pubitemid 351885497)
86. Kentsis A, Gordon RE, Borden KL. Control of biochemical reactions through supramolecular RING domain self-assembly. Proc Natl Acad Sci USA 2002; 99:15404-9. (Pubitemid 35403947)