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

Koh, D. -I., Han, D., Ryu, H., Choi, W.-I., Jeon, B. -N., Kim, M. -K., Kim, Y., Kim, J. Y., Parry, Lee ORCID: https://orcid.org/0000-0002-4467-9196, Clarke, Alan Richard ORCID: https://orcid.org/0000-0002-4281-426X, Reynolds, A. B. and Hur, M. -W. 2014. KAISO, a critical regulator of p53-mediated transcription of CDKN1A and apoptotic genes. Proceedings of the National Academy of Sciences of the United States of America 111 (42) , pp. 15078-15083. 10.1073/pnas.1318780111

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Publisher:	National Academy of Sciences
ISSN:	0027-8424
Date of Acceptance:	15 September 2014
Last Modified:	27 Oct 2022 09:57
URI:	https://orca.cardiff.ac.uk/id/eprint/68297

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