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The mef/elf4 transcription factor fine tunes the DNA damage response.
- Source :
-
Cancer research [Cancer Res] 2011 Jul 15; Vol. 71 (14), pp. 4857-65. Date of Electronic Publication: 2011 May 26. - Publication Year :
- 2011
-
Abstract
- The ATM kinase plays a critical role in initiating the DNA damage response that is triggered by genotoxic stresses capable of inducing DNA double-strand breaks. Here, we show that ELF4/MEF, a member of the ETS family of transcription factors, contributes to the persistence of γH2AX DNA damage foci and promotes the DNA damage response leading to the induction of apoptosis. Conversely, the absence of ELF4 promotes the faster repair of damaged DNA and more rapid disappearance of γH2AX foci in response to γ-irradiation, leading to a radio-resistant phenotype despite normal ATM phosphorylation. Following γ-irradiation, ATM phosphorylates ELF4, leading to its degradation; a mutant form of ELF4 that cannot be phosphorylated by ATM persists following γ-irradiation, delaying the resolution of γH2AX foci and triggering an excessive DNA damage response. Thus, although ELF4 promotes the phosphorylation of H2AX by ATM, its activity must be dampened by ATM-dependent phosphorylation and degradation to avoid an excessive DNA damage response.<br /> (©2011 AACR.)
- Subjects :
- Animals
Ataxia Telangiectasia Mutated Proteins
Cell Cycle Proteins metabolism
DNA genetics
DNA metabolism
DNA radiation effects
DNA-Binding Proteins deficiency
DNA-Binding Proteins genetics
DNA-Binding Proteins radiation effects
Enzyme Activation
Gamma Rays
HEK293 Cells
Histones metabolism
Humans
Mice
Mice, Knockout
NIH 3T3 Cells
Phosphorylation radiation effects
Protein Serine-Threonine Kinases metabolism
Transcription Factors deficiency
Transcription Factors genetics
Transcription Factors radiation effects
Tumor Suppressor Proteins metabolism
DNA Breaks, Double-Stranded
DNA-Binding Proteins metabolism
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 71
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 21616937
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-11-0455