KAISO, a critical regulator of p53-mediated transcription of CDKN1A and apoptotic genes

Title
KAISO, a critical regulator of p53-mediated transcription of CDKN1A and apoptotic genes
Authors
고동인한도현류훈최원일전부남김민경김영수김진영Lee ParryAlan R. ClarkeAlbert B. Reynolds허만욱
Keywords
KAISO; p53; Cell cycle arrest; apoptosis; p300
Issue Date
2014-10
Publisher
Proceedings of the National Academy of Sciences of the United States of America
Citation
VOL 111, NO 42, 15078-15083
Abstract
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.
URI
http://pubs.kist.re.kr/handle/201004/51286
ISSN
00278424
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