1. Methylation-mediated regulation of E2F1 in DNA damage-induced cell death.
- Author
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Xie Q, Bai Y, Wu J, Sun Y, Wang Y, Zhang Y, Mei P, and Yuan Z
- Subjects
- Amino Acid Sequence, Cell Death drug effects, Cell Line, E2F1 Transcription Factor chemistry, E2F1 Transcription Factor genetics, Gene Knockdown Techniques, Histone Demethylases metabolism, Histone-Lysine N-Methyltransferase metabolism, Humans, Lysine metabolism, Methylation drug effects, Molecular Sequence Data, Protein Stability drug effects, Transcription, Genetic drug effects, Tumor Suppressor Protein p53 metabolism, DNA Damage, E2F1 Transcription Factor metabolism
- Abstract
E2F1 promotes DNA damage-induced apoptosis and the post-translational modifications of E2F1 play an important role in the regulation of E2F1-mediated cell death. Here, we found that Set9 and LSD1 regulate E2F1-mediated apoptosis upon DNA damage. Set9 methylates E2F1 at lysine 185, a conserved residue in the DNA-binding domain of E2F family proteins. The methylation of E2F1 by Set9 leads to the stabilization of E2F1 and up-regulation of its proapoptotic target genes p73 and Bim, and thereby induces E2F1-mediated apoptosis in response to genotoxic agents. We also found that LSD1 demethylates E2F1 at lysine 185 and reduces E2F1-mediated cell death. The identification of the methylation/demethylation of E2F1 by Set9/LSD1 suggests that E2F1 is dynamically regulated by epigenetic enzymes in response to DNA damage.
- Published
- 2011
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