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Mol Cell. 2005 May 27;18(5):577-87.

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

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1
Signal Transduction Program, The Burnham Institute, La Jolla, California 92037, USA.

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.

PMID:
15916964
PMCID:
PMC2954254
DOI:
10.1016/j.molcel.2005.04.015
[Indexed for MEDLINE]
Free PMC Article

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