Destabilizing missense mutations in the tumour suppressor protein p53 enhance its ubiquitination in vitro and in vivo

Biochemical Journal

Volumn 397, Issue 2, 2006, Pages 355-367

  Shimizu, Harumi ^a,b   Saliba, David ^a   Wallace, Maura ^a   Finlan, Lee ^a   Langridge Smith, Patrick R R ^a   Hupp, Ted R ^a  

^a UNIVERSITY OF EDINBURGH   (United Kingdom)

^b GENENTECH INC   (United States)

Author keywords

Chaperone; Murine double minute clone 2 oncoprotein (MDM2); p53; Protein folding; Ubiquitin

Indexed keywords

ANTIBODIES; CLONING; DNA; IMMUNOLOGY; MUTAGENESIS; PROTEINS;

CHAPERONE; MURINE DOUBLE MINUTE CLONE 2 ONCOPROTEIN (MDM2); P53; PROTEIN FOLDING; UBIQUITIN;

TUMORS;

DOCKING PROTEIN; EPITOPE; LYSINE; OLIGOMER; PROTEIN ANTIBODY; PROTEIN MDM2; PROTEIN P53; UBIQUITIN ANTIBODY; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; UBIQUITIN;

ARTICLE; CHIMERA; CONTROLLED STUDY; DNA BINDING; HUMAN; HUMAN CELL; IMMUNOBLOTTING; IMMUNOPRECIPITATION; IN VITRO STUDY; IN VIVO STUDY; MISSENSE MUTATION; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN MODIFICATION; UBIQUITINATION; WILD TYPE; CELL FREE SYSTEM; CHEMICAL STRUCTURE; GENETIC TRANSFECTION; GENETICS; METABOLISM; MUTATION; PROTEIN MOTIF; PROTEIN SECONDARY STRUCTURE; TUMOR CELL LINE;

MURINAE;

AMINO ACID MOTIFS; CELL LINE, TUMOR; CELL-FREE SYSTEM; HUMANS; MODELS, MOLECULAR; MUTATION; MUTATION, MISSENSE; PROTEIN CONFORMATION; PROTEIN STRUCTURE, SECONDARY; PROTO-ONCOGENE PROTEINS C-MDM2; TRANSFECTION; TUMOR SUPPRESSOR PROTEIN P53; UBIQUITIN;

EID: 33745951312     PISSN: 02646021     EISSN: None     Source Type: Journal    
DOI: 10.1042/BJ20051521     Document Type: Article

References (55)

1. Vogelstein, B. and Kinzler, K. W. (2004) Cancer genes and the pathways they control. Nat. Med. 10, 789-799
2. Honda, R., Tanaka, H. and Yasuda, H. (1997) Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett. 420, 25-27
3. Kubbutat, M. H., Jones, S. N. and Vousden, K. H. (1997) Regulation of p53 stability by Mdm2. Nature (London) 387, 299-303
4. Haupt, Y., Maya, R., Kazaz, A. and Oren, M. (1997) Mdm2 promotes the rapid degradation of p53. Nature (London) 387, 296-299
5. Leng, R. P., Lin, Y., Ma, W., Wu, H., Lemmers, B., Chung, S., Parant, J. M., Lozano, G., Hakem, R. and Benchimol, S. (2003) Pirh2, a p53-induced ubiquitin-protein iigase, promotes p53 degradation. Cell 112, 779-791
6. Dornan, D., Wertz, I., Shimizu, H., Arnott, D., Frantz, G. D., Dowd, P., O'Rourke, K., Koeppen, H. and Dixit, V. M. (2004) The ubiquitin ligase COP1 is a critical negative regulator of p53. Nature (London) 429, 86-92
7. Esser, C., Scheffner, M. and Hohfeld, J. (2005) The chaperone-associated ubiquitin ligase CHIP is able to target p53 for proteasomal degradation. J. Biol. Chem. 280, 27443-27448
8. Iyer, N. G., Chin, S. F., Ozdag, H., Daigo, Y., Hu, D. E., Cariati, M., Brindle, K., Aparicio, S. and Caldas, C. (2004) p300 regulates p53-dependent apoptosis after DNA damage in colorectal cancer cells by modulation of PUMA/p21 levels. Proc. Natl. Acad. Sci. U.S.A. 101, 7386-7391
9. Shimizu, H. and Hupp, T. R. (2003) Intrasteric regulation of MDM2, Trends Biochem. Sci. 28, 346-349
10. Knights, C. D., Liu, Y., Appella, E. and Kulesz-Martin, M. (2003) Defective p53 post-translational modification required for wild type p53 inactivation in malignant epithelial cells with mdm2 gene amplification. J. Biol. Chem. 278, 52890-52900
11. Thut, C. J., Goodrich, J. A. and Tjian, R. (1997) Repression of p53-mediated transcription by MDM2: a dual mechanism. Genes Dev. 11, 1974-1986
12. Lin, J., Chen, J., Elenbaas, B. and Levine, A. J. (1994) Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev. 8, 1235-1246
13. Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J. and Pavletich, N. P. (1996) Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274, 948-953
14. Picksley, S. M., Vojtesek, B., Sparks, A. and Lane, D. P. (1994) Immunochemical analysis of the interaction of p53 with MDM2: fine mapping of the MDM2 binding site on p53 using synthetic peptides. Oncogene 9, 2523-2529
15. Lai, Z., Ferry, K. V., Diamond, M. A., Wee, K. E., Kim, Y. B., Ma, J., Yang, T., Benfield, P. A., Copeland, R. A. and Auger, K. R. (2001) Human mdm2 mediates multiple mono-ubiquitination of p53 by a mechanism requiring enzyme isomerization. J. Biol. Chem. 276, 31357-31367
16. Stimueli, A. and Oren, M. (2004) Regulation of p53 by Mdm2: fate is in the numbers. Mol. Cell 13, 4-5
17. Lai, Z., Yang, T., Kim, Y. B., Sielecki, T. M., Diamond, M. A., Strack, P., Rolfe, M., Caligiuri, M., Benfield, P. A., Auger, K. R. and Copeland, R. A. (2002) Differentiation of Hdm2-mediated p53 ubiquitination and Hdm2 autoubiquitination activity by small molecular weight inhibitors. Proc. Natl. Acad. Sci. U.S.A. 99, 14734-14739
18. Vassilev, L. T. (2004) Small-molecule antagonists of p53-MDM2 binding: research tools and potential therapeutics. Cell Cycle 3, 419-421
19. Kubbutat, M. H., Ludwig, R. L., Ashcroft, M. and Vousden, K. H. (1998) Regulation of Mdm2-directed degradation by the C terminus of p53. Mol. Cell. Biol. 18, 5690-5698
20. Marston, N. J., Jenkins, J. R. and Vousden, K. H. (1995) Oligomerisation of full length p53 contributes to the interaction with mdm2 but not HPV E6. Oncogene 10, 1709-1715
21. Maki, C. G. (1999) Oligomerization is required for p53 to be efficiently ubiquitinated by MDM2. J. Biol. Chem. 274, 16531-16535
22. Shimizu, H., Burch, L. R., Smith, A. J., Dornan, D., Wallace, M., Ball, K. L. and Hupp, T. R. (2002) The conformationally flexible S9-S10 linker region in the core domain of p53 contains a novel MDM2 binding site whose mutation increases ubiquitination of p53 in vivo. J. Biol. Chem. 277, 28446-28458
23. Burch, L., Shimizu, H., Smith, A., Patterson, C. and Hupp, T. R. (2004) Expansion of protein interaction maps by phage peptide display using MDM2 as a prototypical conformationally flexible target protein. J. Mol. Biol. 337, 129-145
24. Vojtesek, B., Dolezalova, H., Lauerova, L., Svitakova, M., Havlis, P., Kovarik, J., Midgley, C. A. and Lane, D. P. (1995) Conformational changes in p53 analysed using new antibodies to the core DNA binding domain of the protein. Oncogene 10, 389-393
25. Dornan, D., Shimizu, H., Burch, L., Smith, A. J. and Hupp, T. R. (2003) The proline repeat domain of p53 binds directly to the transcriptional coactivator p300 and allosterically controls DNA-dependent acetylation of p53. Mol. Cell. Biol. 23, 8846-8861
26. Milner, J. and Medcalf, E. A. (1990) Temperature-dependent switching between "wild-type" and "mutant" forms of p53-Val135. J. Mol. Biol. 216, 481-484
27. Milner, J. and Medcalf, E. A. (1991) Cotranslation of activated mutant p53 with wild type drives the wild-type p53 protein into the mutant conformation. Cell 65, 765-774
28. Milner, J., Medcalf, E. A. and Cook, A. C. (1991) Tumor suppressor p53: analysis of wild-type and mutant p53 complexes. Mol. Cell. Biol. 11, 12-19
29. Nikolaev, A. Y., Li, M., Puskas, N., Qin, J. and Gu, W. (2003) Parc: a cytoplasmic anchor for p53. Cell 112, 29-40
30. Lin, W. C. and Desiderio, S. (1993) Regulation of V(D)J recombination activator protein RAG-2 by phosphorylation. Science 260, 953-959
31. Dyson, H. J. and Wright, P. E. (2002) Coupling of folding and binding for unstructured proteins. Curr. Opin. Struct. Biol. 12, 54-60
32. Lane, D. P. and Hupp, T. R. (2003) Drug discovery and p53. Drug Discov. Today 8, 347-355
33. Bell, S., Klein, C., Muller, L., Hansen, S. and Buchner, J. (2002) p53 contains large unstructured regions in its native state. J. Mol. Biol. 322, 917-927
34. Nichols, N. M. and Matthews, K. S. (2002) Human p53 phosphorylation mimic, S392E, increases nonspecific DNA affinity and thermal stability. Biochemistry 41, 170-178
35. Bullock, A. N. and Fersht, A. R. (2001) Rescuing the function of mutant p53. Nat. Rev. Cancer 1, 68-76
36. Brown, C. R., Hong-Brown, L. Q. and Welch, W. J. (1997) Correcting temperature-sensitive protein folding defects. J. Clin. Invest. 99, 1432-1444
37. Xirodimas, D. P., Seville, M. K., Bourdon, J. C., Hay, R. T. and Lane, D. P. (2004) Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity. Cell 118, 83-97
38. Rodriguez, M. S., Desterro, J. M., Lain, S., Lane, D. P. and Hay, R. T. (2000) Multiple C-terminal lysine residues target p53 for ubiquitin-proteasome- mediated degradation. Mol. Cell. Biol. 20, 8458-8467
39. Dornan, D., Eckert, M., Wallace, M., Shimizu, H., Ramsay, E., Hupp, T. R. and Ball, K. L. (2004) Interferon regulatory factor 1 binding to p300 stimulates DNA-dependent acetylation of p53. Mol. Cell. Biol. 24, 10083-10098
40. Stephen, C. W., Helminen, P. and Lane, D. P. (1995) Characterisation of epitopes on human p53 using phage-displayed peptide libraries: insights into antibody-peptide interactions. J. Mol. Biol. 248, 58-78
41. Hupp, T. R. and Lane, D. P. (1994) Allosteric activation of latent p53 tetramers. Curr. Biol. 4, 865-875
42. Vousden, K. H. and Lu, X. (2002) Live or let die: the cell's response to p53. Nat. Rev. Cancer 2, 594-604
43. Linares, L. K. and Schetfner, M. (2003) The ubiquitin-protein ligase activity of Hdm2 is inhibited by nucleic acids. FEBS Lett. 554, 73-76
44. Dawson, R., Muller, L., Dehner, A., Klein, C., Kessler, H. and Buchner, J. (2003) The N-terminal domain of p53 is natively unfolded. J. Mol. Biol. 332, 1131-1141
45. Peng, Y., Chen, L., Li, C., Lu, W. and Chen, J. (2001) Inhibition of MDM2 by hsp90 contributes to mutant p53 stabilization. J. Biol. Chem. 276, 40583-40590
46. Beitel, L. K., Elhaji, Y. A., Lumbroso, R., Wing, S. S., Panel-Raymond, V., Gottlieb, B., Pinsky, L. and Trifiro, M. A. (2002) Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity. J. Mol. Endocrinol. 29, 41-60
47. McDonough, H. and Patterson, C. (2003) CHIP: a link between the chaperone and proteasome systems. Cell Stress Chaperones 8, 303-308
48. Camus, S., Higgins, M., Lane, D. P. and Lain, S. (2003) Differences in the ubiquitination of p53 by Mdm2 and the HPV protein E6. FEBS Lett. 536, 220-224
49. Breitschopf, K., Bengal, E., Ziv, T., Admon, A. and Ciechanover, A. (1998) A novel site for ubiquitination: the N-terminal residue, and not internal lysines of MyoD, is essential for conjugation and degradation of the protein. EMBO J. 17, 5964-5973
50. Aviel, S., Winberg, G., Massucci, M. and Ciechanover, A. (2000) Degradation of the Epstein-Barr virus latent membrane protein 1 (LMP1) by the ubiquitin-proteasome pathway. Targeting via ubiquitination of the N-terminal residue. J. Biol. Chem. 275, 23491-23499
51. Reinstein, E., Scheffner, M., Oren, M., Ciechanover, A. and Schwartz, A. (2000) Degradation of the E7 human papillomavirus oncoprotein by the ubiquitin-proteasome system: targeting via ubiquitination of the N-terminal residue. Oncogene 19, 5944-5950
52. Connell, P., Ballinger, C. A., Jiang, J., Wu, Y., Thompson, L. J., Hohfeld, J. and Patterson, C. (2001) The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat. Cell. Biol. 3, 93-96
53. Cyr, D. M., Hohfeld, J. and Patterson, C. (2002) Protein quality control: U-box-containing E3 ubiquitin ligases join the fold. Trends Biochem. Sci. 27, 368-375
54. Meacham, G. C., Patterson, C., Zhang, W., Younger, J. M. and Cyr, D. M. (2001) The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat. Cell Biol. 3, 100-105
55. Yu, G., Rudiger, S., Veprintsev, D., Freund, S., Fernandez-Fernandez, M. and Fersht, A. R. (2006) The central region of HDM2 provides a second binding site for p53. Proc. Natl. Acad. Sci. U.S.A. 103, 1227-1232