DNA-dependent protein kinase-independent activation of p53 in response to DNA damage Journal Article
| Authors: | Burma, S.; Kurimasa, A.; Xie, G.; Taya, Y.; Araki, R.; Abe, M.; Crissman, H. A.; Ouyang, H.; Li, G. C.; Chen, D. J. |
| Article Title: | DNA-dependent protein kinase-independent activation of p53 in response to DNA damage |
| Abstract: | Phosphorylation at serine 15 of the human p53 tumor suppressor protein is induced by DNA damage and correlates with accumulation of p53 and its activation as a transcription factor. The DNA-dependent protein kinase (DNA- PK) can phosphorylate serine 15 of human p53 and the homologous serine 18 of murine p53 in vitro. Contradictory reports exist about the requirement for DNA-PK in vivo for p53 activation and cell cycle arrest in response to ionizing radiation. While primary SCID (severe combined immunodeficiency) cells, that have defective DNA-PK, show normal p53 activation and cell cycle arrest, a transcriptionally inert form of p53 is induced in the SCID cell line SCGR11. In order to unambiguously define the role of the DNA-PK catalytic subunit (DNA-PKcs) in p53 activation, we examined p53 phosphorylation in mouse embryonic fibroblasts (MEFs) from DNA-PKcs-null mice. We found a similar pattern of serine 18 phosphorylation and accumulation of p53 in response to irradiation in both control and DNA-PKcs- null MEFs. The induced p53 was capable of sequence-specific DNA binding even in the absence of DNA-PKcs. Transactivation of the cyclin-dependent-kinase inhibitor p21, a downstream target of p53, and the G1 cell cycle checkpoint were also found to be normal in the DNA-PKcs -/- MEFs. Our results demonstrate that DNA-PKcs, unlike the related ATM protein, is not essential for the activation of p53 and G1 cell cycle arrest in response to ionizing radiation. |
| Keywords: | controlled study; protein phosphorylation; dna-binding proteins; nonhuman; animal cell; mouse; animals; mice; dna damage; embryo; protein dna binding; cell line; mice, mutant strains; protein binding; mice, scid; phosphorylation; protein p53; transcription factors; dna; protein-serine-threonine kinases; transactivation; fibroblasts; ionizing radiation; protein induction; tumor suppressor protein p53; cyclin-dependent kinase inhibitor p21; up-regulation; cyclins; protein p21; protein kinase; cell cycle g1 phase; g1 phase; phosphoserine; gamma rays; dna-activated protein kinase; priority journal; article |
| Journal Title: | Journal of Biological Chemistry |
| Volume: | 274 |
| Issue: | 24 |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Date Published: | 1999-06-11 |
| Start Page: | 17139 |
| End Page: | 17143 |
| Language: | English |
| DOI: | 10.1074/jbc.274.24.17139 |
| PUBMED: | 10358069 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 16 August 2016 -- Source: Scopus |
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