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PMID: 15916964 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, P.H.S.

ATM-dependent phosphorylation of ATF2 is required for the DNA damage response.

Molecular cell ·Vol. 18 ·No. 5 ·2005-05-27 ·Pages 577-87

Bhoumik A, Takahashi S, Breitweiser W, Shiloh Y, Jones N, Ronai Z

Abstract

Activating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines 490 and 498 following ionizing radiation (IR). Phosphoantibodies to ATF2(490/8) reveal dose- and time-dependent phosphorylation of ATF2 by ATM that results in its rapid colocalization with gamma-H2AX and MRN components into IR-induced foci (IRIF). Inhibition of ATF2 expression decreased recruitment of Mre11 to IRIF, abrogated S phase checkpoint, reduced activation of ATM, Chk1, and Chk2, and impaired radioresistance. ATF2 requires neither JNK/p38 nor its DNA binding domain for recruitment to IRIF and the S phase checkpoint. Our findings identify a role for ATF2 in the DNA damage response that is uncoupled from its transcriptional activity.

MeSH Terms
Activating Transcription Factor 2 Amino Acid Sequence Animals Antibodies, Phospho-Specific/metabolism Ataxia Telangiectasia Mutated Proteins Cell Cycle Proteins/genetics,metabolism Cell Line Checkpoint Kinase 1 Checkpoint Kinase 2 Cyclic AMP Response Element-Binding Protein/genetics,metabolism DNA Damage DNA Repair DNA Repair Enzymes DNA-Binding Proteins/genetics,metabolism Fibroblasts/cytology,physiology Histones/metabolism Humans MRE11 Homologue Protein Mice Molecular Sequence Data Nuclear Proteins/metabolism Phosphorylation Protein Kinases/metabolism Protein Serine-Threonine Kinases/genetics,metabolism RNA Interference Radiation, Ionizing Sequence Alignment Serine/metabolism Transcription Factors/genetics,metabolism Transcription, Genetic Tumor Suppressor Proteins/genetics,metabolism
Chemicals
ATF2 protein, human Activating Transcription Factor 2 Antibodies, Phospho-Specific Atf2 protein, mouse Cell Cycle Proteins Cyclic AMP Response Element-Binding Protein DNA-Binding Proteins H2AX protein, human Histones MRE11 protein, human Mre11a protein, mouse NBN protein, human Nuclear Proteins Transcription Factors Tumor Suppressor Proteins Serine Protein Kinases Checkpoint Kinase 2 ATM protein, human Ataxia Telangiectasia Mutated Proteins Atm protein, mouse CHEK1 protein, human CHEK2 protein, human Checkpoint Kinase 1 Chek1 protein, mouse Chek2 protein, mouse Protein Serine-Threonine Kinases MRE11 Homologue Protein DNA Repair Enzymes
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bhoumik Anindita
Signal Transduction Program, The Burnham Institute, La Jolla, California 92037, USA.
Takahashi Shoichi
Breitweiser Wolfgang
Shiloh Yosef
Jones Nic
Ronai Ze'ev
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Article Info
Journal
Molecular cell
Abbr.
Mol Cell
ISSN
1097-2765
DOI
10.1016/j.molcel.2005.04.015
Published
2005-05-27
Pages
577-87
Language
English
Region
United States
NLM ID
9802571
PMCID
PMC2954254
Subset
IM
Grants
NCI NIH HHS · R01 CA051995 · United States
NCI NIH HHS · R01 CA099961 · United States
NCI NIH HHS · CA 51995 · United States
NCI NIH HHS · R01 CA117927 · United States
NCI NIH HHS · R01 CA117927-01 · United States
External Links
PubMed source DOI: 10.1016/j.molcel.2005.04.015 PMC Full Text View journal details
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