Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/38698
Title: Human EHMT2/G9a activates p53 through methylation-independent mechanism
Authors: Rada, Miran
Vasileva, Elena
Lezina, Larissa
Marouco, Diana
Antonov, Alexey V.
Macip, Salvador
Melino, Gerry
Barlev, Nickola A.
First Published: 25-Jul-2016
Publisher: Nature Publishing Group
Citation: Oncogene, 2016, in press
Abstract: p53 is a critical tumor suppressor in humans. It functions mostly as a transcriptional factor and its activity is regulated by numerous post-translational modifications. Among different covalent modifications found on p53 the most controversial one is lysine methylation. We found that human G9a (hG9a) unlike its mouse orthologue (mG9a) potently stimulated p53 transcriptional activity. Both ectopic and endogenous hG9a augmented p53-dependent transcription of pro-apoptotic genes, including Bax and Puma, resulting in enhanced apoptosis and reduced colony formation. Significantly, shRNA-mediated knockdown of hG9a attenuated p53-dependent activation of Puma. On the molecular level, hG9a interacted with histone acetyltransferase, p300/CBP, resulting in increased histone acetylation at the promoter of Puma. The bioinformatics data substantiated our findings showing that positive correlation between G9a and p53 expression is associated with better survival of lung cancer patients. Collectively, this study demonstrates that depending on the cellular and organismal context, orthologous proteins may exert both overlapping and opposing functions. Furthermore, this finding has important ramifications on the use of G9a inhibitors in combination with genotoxic drugs to treat p53-positive tumors.Oncogene advance online publication, 25 July 2016; doi:10.1038/onc.2016.258.
DOI Link: 10.1038/onc.2016.258
ISSN: 0950-9232
eISSN: 1476-5594
Links: http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2016258a.html
http://hdl.handle.net/2381/38698
Version: Post-print
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © Nature Publishing Group, 2016. This version of the article is distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Description: Following the embargo period the above license applies.
Appears in Collections:Published Articles, Dept. of Biochemistry

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