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

2.50
Hdl Handle:
http://hdl.handle.net/10541/74814
Title:
ATM-dependent phosphorylation of ATF2 is required for the DNA damage response.
Authors:
Bhoumik, Anindita; Takahashi, Shoichi; Shiloh, Yosef; Jones, Nic; Ronai, Ze'ev; Breitwieser, Wolfgang
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.
Affiliation:
Signal Transduction Program, The Burnham Institute, La Jolla, California 92037, USA.
Citation:
ATM-dependent phosphorylation of ATF2 is required for the DNA damage response. 2005, 18 (5):577-87 Mol. Cell
Journal:
Molecular Cell
Issue Date:
27-May-2005
URI:
http://hdl.handle.net/10541/74814
DOI:
10.1016/j.molcel.2005.04.015
PubMed ID:
15916964
Type:
Article
Language:
en
ISSN:
1097-2765
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorBhoumik, Anindita-
dc.contributor.authorTakahashi, Shoichi-
dc.contributor.authorShiloh, Yosef-
dc.contributor.authorJones, Nic-
dc.contributor.authorRonai, Ze'ev-
dc.contributor.authorBreitwieser, Wolfgang-
dc.date.accessioned2009-07-21T16:35:19Z-
dc.date.available2009-07-21T16:35:19Z-
dc.date.issued2005-05-27-
dc.identifier.citationATM-dependent phosphorylation of ATF2 is required for the DNA damage response. 2005, 18 (5):577-87 Mol. Cellen
dc.identifier.issn1097-2765-
dc.identifier.pmid15916964-
dc.identifier.doi10.1016/j.molcel.2005.04.015-
dc.identifier.urihttp://hdl.handle.net/10541/74814-
dc.description.abstractActivating 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.en
dc.language.isoenen
dc.subject.meshActivating Transcription Factor 2-
dc.subject.meshAmino Acid Sequence-
dc.subject.meshAnimals-
dc.subject.meshAntibodies, Phospho-Specific-
dc.subject.meshCell Cycle Proteins-
dc.subject.meshCell Line-
dc.subject.meshCyclic AMP Response Element-Binding Protein-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Repair-
dc.subject.meshDNA Repair Enzymes-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFibroblasts-
dc.subject.meshHistones-
dc.subject.meshHumans-
dc.subject.meshMice-
dc.subject.meshMolecular Sequence Data-
dc.subject.meshNuclear Proteins-
dc.subject.meshPhosphorylation-
dc.subject.meshProtein Kinases-
dc.subject.meshProtein-Serine-Threonine Kinases-
dc.subject.meshRNA Interference-
dc.subject.meshRadiation, Ionizing-
dc.subject.meshSequence Alignment-
dc.subject.meshSerine-
dc.subject.meshTranscription Factors-
dc.subject.meshTranscription, Genetic-
dc.subject.meshTumor Suppressor Proteins-
dc.titleATM-dependent phosphorylation of ATF2 is required for the DNA damage response.en
dc.typeArticleen
dc.contributor.departmentSignal Transduction Program, The Burnham Institute, La Jolla, California 92037, USA.en
dc.identifier.journalMolecular Cellen

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