KAISO, a critical regulator of p53-mediated transcription of CDKN1A and apoptotic genes
- KAISO, a critical regulator of p53-mediated transcription of CDKN1A and apoptotic genes
- 고동인; 한도현; 류훈; 최원일; 전부남; 김민경; 김영수; 김진영; Lee Parry; Alan R. Clarke; Albert B. Reynolds; 허만욱
- KAISO; p53; Cell cycle arrest; apoptosis; p300
- Issue Date
- Proceedings of the National Academy of Sciences of the United States of America
- VOL 111, NO 42, 15078-15083
- An unresolved issue in genotoxic stress response is identification of induced regulatory proteins and how these activate tumor suppressor p53 to determine appropriate cell responses. Transcription factor KAISO was previously described to repress transcription following binding to methylated DNA. In this study, we show that KAISO is induced by DNA damage in p53-expressing cells and then interacts with the p53-p300 complex to increase acetylation of p53 K320 and K382 residues, although decreasing K381 acetylation. Moreover, the p53 with this particular acetylation pattern shows increased DNA binding and potently induces cell cycle arrest and apoptosis by activating transcription of CDKN1A (cyclin-dependent kinase inhibitor 1) and various apoptotic genes. Analogously, in Kaiso KO mouse embryonic fibroblast cells, p53-to-promoter binding and up-regulation of p21 and apoptosis gene expression is significantly compromised. KAISO may therefore be a critical regulator of p53-mediated cell cycle arrest and apoptosis in response to various genotoxic stresses in mammalian cells.
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