Ser46 phosphorylation of p53 is not always sufficient to induce apoptosis: Multiple mechanisms of regulation of p53-dependent apoptosis

Genes to Cells

Volumn 12, Issue 7, 2007, Pages 853-861

  Kurihara, Akira ^a   Nagoshi, Hirokazu ^a   Yabuki, Masato ^a   Okuyama, Ryuhei ^b   Obinata, Masuo ^a   Ikawa, Shuntaro ^a  

^a TOHOKU UNIVERSITY   (Japan)

^b TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE; DOXORUBICIN; GLUTAMIC ACID; PROTEIN P53; APOPTOSIS REGULATORY PROTEIN; DNA BINDING PROTEIN; NUCLEAR PROTEIN; PROTEIN SERINE THREONINE KINASE; SERINE; TUMOR SUPPRESSOR PROTEIN; TUMOR SUPPRESSOR PROTEIN P73; UNCLASSIFIED DRUG;

AMINO ACID SUBSTITUTION; APOPTOSIS; ARTICLE; CELL AGING; CELL STRAIN MCF 7; CONTROLLED STUDY; GENE EXPRESSION; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REGULATORY MECHANISM; CELL CULTURE; CELL STRAIN HCT116; CHEMISTRY; DRUG EFFECT; GENETICS; METABOLISM; PHOSPHORYLATION; PHYSIOLOGY; TRANSACTIVATION;

APOPTOSIS; APOPTOSIS REGULATORY PROTEINS; CELL AGING; DNA-BINDING PROTEINS; DOXORUBICIN; HCT116 CELLS; HUMANS; NUCLEAR PROTEINS; PHOSPHORYLATION; PROTEIN-SERINE-THREONINE KINASES; SERINE; TRANS-ACTIVATION (GENETICS); TUMOR CELLS, CULTURED; TUMOR SUPPRESSOR PROTEIN P53; TUMOR SUPPRESSOR PROTEINS;

EID: 34250729019     PISSN: 13569597     EISSN: 13652443     Source Type: Journal    
DOI: 10.1111/j.1365-2443.2007.01097.x     Document Type: Article

References (27)

1. Ashcroft, M., Kubbutat, M.H. & Vousden, K.H. (1999) Regulation of p53 function and stability by phosphorylation. Mol. Cell. Biol. 19, 1751-1758.
2. Bode, A.M. & Dong, Z. (2004) Post-translational modification of p53 in tumorigenesis. Nat. Rev. Cancer 4, 793-805.
3. Chao, C., Saito, S., Kang, J., Anderson, C.W., Appella, E. & Xu, Y. (2000) p53 transcriptional activity is essential for p53-dependent apoptosis following DNA damage. EMBO J. 19, 4967-4975.
4. Chipuk, J.E., Bouchier-Hayes, L., Kuwana, T., Newmeyer, D.D. & Green, D.R. (2005) PUMA couples the nuclear and cytoplasmic proapoptotic function of p53. Science 309, 1732-1735.
5. D'Orazi, G., Cecchinelli, B., Bruno, T., Manni, I., Higashimoto, Y., Saito, S., Gostissa, M., Coen, S., Marchetti, A., Del Sal, G., Piaggio, G., Fanciulli, M., Appella, E. & Soddu, S. (2002) Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis. Nat. Cell Biol. 4, 11-19.
6. Erster, S., Mihara, M., Kim, R.H., Petrenko, O. & Moll, U.M. (2004) In vivo mitochondrial p53 translocation triggers a rapid first wave of cell death in response to DNA damage that can precede p53 target gene activation. Mol. Cell. Biol. 24, 6728-6741.
7. Feng, L., Hollstein, M. & Xu, Y. (2006) Ser46 phosphorylation regulates p53-dependent apoptosis and replicative senescence. Cell Cycle 5, 2812-2819.
8. Gudkov, A.V. & Komarova, E.A. (2003) The role of p53 in determining sensitivity to radiotherapy. Nat. Rev. Cancer 3, 117-129.
9. Harms, K., Nozell, S. & Chen, X. (2004) The common and distinct target genes of the p53 family transcription factors. Cell. Mol. Life Sci. 61, 822-842.
10. Hofmann, T.G., Moller, A., Sirma, H., Zentgraf, H., Taya, Y., Droge, W., Will, H. & Schmitz, M.L. (2002) Regulation of p53 activity by its interaction with homeodomain-interacting protein kinase-2. Nat. Cell Biol. 4, 1-10.
11. Hollstein, M., Rice, K., Greenblatt, M.S., Soussi, T., Fuchs, R., Sorlie, T., Hovig, E., Smith-Sorensen, B., Montesano, R. & Harris, C.C. (1994) Database of p53 gene somatic mutations in human tumors and cell lines. Nucleic Acids Res. 22, 3551-3555.
12. Hollstein, M., Sidransky, D., Vogelstein, B. & Harris, C.C. (1991) p53 mutations in human cancers. Science 253, 49-53.
13. Huang, L.C., Clarkin, K.C. & Wahl, G.M. (1996) Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest. Proc. Natl. Acad. Sci. USA 93, 4827-4832.
14. Ishimoto, O., Kawahara, C., Enjo, K., Obinata, M., Nukiwa, T. & Ikawa, S. (2002) Possible oncogenic potential of DeltaNp73: A newly identified isoform of human p73. Cancer Res. 62, 636-641.
15. Jimenez, G.S., Nister, M., Stommel, J.M., Beeche, M., Barcarse, E.A., Zhang, X.Q., O'Gorman, S. & Wahl, G.M. (2000) A transactivation-deficient mouse model provides insights into Trp53 regulation and function. Nat. Genet. 26, 37-43.
16. Kim, K., Choi, K.H., Fu, Y.M., Meadows, G.G. & Joe, C.O. (2003) Dephosphorylation of p53 during cell death by N-α-tosyl- l -phenylalanyl chloromethyl ketone. Biochem. Biophys. Res. Commun. 306, 954-958.
17. Levine, A.J. (1997) p53, the cellular gatekeeper for growth and division. Cell 88, 323-331.
18. Li, X., Dumont, P., Della Pietra, A., Shetler, C. & Murphy, M.E. (2005) The codon 47 polymorphism in p53 is functionally significant. J. Biol. Chem. 280, 24245-24251.
19. Lowe, S.W., Schmitt, E.M., Smith, S.W., Osborne, B.A. & Jacks, T. (1993) p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 362, 847-849.
20. Melino, G., Lu, X., Gasco, M., Crook, T. & Knight, R.A. (2003) Functional regulation of p73 and p63: Development and cancer. Trends Biochem. Sci. 28, 663-670.
21. Mihara, M., Erster, S., Zaika, A., Petrenko, O., Chittenden, T., Pancoska, P. & Moll, U.M. (2003) p53 has a direct apoptogenic role at the mitochondria. Mol. Cell 11, 577-590.
22. Oda, K., Arakawa, H., Tanaka, T., Matsuda, K., Tanikawa, C., Mori, T., Nishimori, H., Tamai, K., Tokino, T., Nakamura, Y. & Taya, Y. (2000) p53AIP1, a potential mediator of p53-dependent apoptosis, and its regulation by Ser-46-phosphorylated p53. Cell 102, 849-862.
23. Saito, S., Yamaguchi, H., Higashimoto, Y., Chao, C., Xu, Y., Fornace, A.J., Jr., Appella, E. & Anderson, C.W. (2003) Phosphorylation site interdependence of human p53 post-translational modifications in response to stress. J. Biol. Chem. 278, 37536-37544.
24. Shieh, S.Y., Ikeda, M., Taya, Y. & Prives, C. (1997) DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 91, 325-334.
25. Shieh, S.Y., Taya, Y. & Prives, C. (1999) DNA damage-inducible phosphorylation of p53 at N-terminal sites including a novel site, Ser20, requires tetramerization. EMBO J. 18, 1815-1823.
26. Thompson, T., Tovar, C., Yang, H., Carvajal, D., Vu, B.T., Xu, Q., Wahl, G.M., Heimbrook, D.C. & Vassilev, L.T. (2004) Phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis. J. Biol. Chem. 279, 53015-53022.
27. Vousden, K.H. & Lu, X. (2002) Live or let die: The cell's response to p53. Nat. Rev. Cancer 2, 594-604.