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E2F1 transcription is induced by genotoxic stress through ATM/ATR activation
Author(s) -
Carcagno Abel L.,
Ogara María F.,
Sonzogni Silvina V.,
Marazita Mariela C.,
Sirkin Pablo F.,
Ceruti Julieta M.,
Cánepa Eduardo T.
Publication year - 2009
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1002/iub.197
Subject(s) - e2f1 , dna damage , transcription (linguistics) , e2f , transcription factor , biology , cell cycle , microbiology and biotechnology , gene , dna , cancer research , genetics , linguistics , philosophy
E2F1, a member of the E2F family of transcription factors, plays a critical role in controlling both cell cycle progression and apoptotic cell death in response to DNA damage and oncogene activation. Following genotoxic stresses, E2F1 protein is stabilized by phosphorylation and acetylation driven to its accumulation. The aim of the present work was to examine whether the increase in E2F1 protein levels observed after DNA damage is only a reflection of an increase in E2F1 protein stability or is also the consequence of enhanced transcription of the E2F1 gene. The data presented here demonstrates that UV light and other genotoxics induce the transcription of E2F1 gene in an ATM/ATR dependent manner, which results in increasing E2F1 mRNA and protein levels. After genotoxic stress, transcription of cyclin E, an E2F1 target gene, was significantly induced. This induction was the result of two well‐differentiated effects, one of them dependent on de novo protein synthesis and the other on the protein stabilization. Our results strongly support a transcriptional effect of DNA damaging agents on E2F1 expression. The results presented herein uncover a new mechanism involving E2F1 in response to genotoxic stress. © 2009 IUBMB IUBMB Life, 61(5): 537–543, 2009