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

Molecular cell | May 27, 2005

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.

Pubmed ID: 15916964 RIS Download

Mesh terms: Activating Transcription Factor 2 | Amino Acid Sequence | Animals | Antibodies, Phospho-Specific | Ataxia Telangiectasia Mutated Proteins | Cell Cycle Proteins | Cell Line | Checkpoint Kinase 1 | Checkpoint Kinase 2 | Cyclic AMP Response Element-Binding Protein | DNA Damage | DNA Repair | DNA Repair Enzymes | DNA-Binding Proteins | Fibroblasts | Histones | Humans | Mice | Molecular Sequence Data | Nuclear Proteins | Phosphorylation | Protein Kinases | Protein-Serine-Threonine Kinases | RNA Interference | Radiation, Ionizing | Sequence Alignment | Serine | Transcription Factors | Transcription, Genetic | Tumor Suppressor Proteins

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Associated grants

  • Agency: NCI NIH HHS, Id: R01 CA051995
  • Agency: NCI NIH HHS, Id: R01 CA099961
  • Agency: NCI NIH HHS, Id: CA 51995
  • Agency: NCI NIH HHS, Id: R01 CA117927
  • Agency: NCI NIH HHS, Id: R01 CA117927-01

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