ATM and Chk2 kinase target the p53 cofactor Strap.

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Cassandra J Adams, Anne L Graham, Martin Jansson, Amanda S Coutts, Mariola Edelmann, Linda Smith, Benedikt Kessler, Nicholas B La Thangue

The p53 cofactor Strap (stress responsive activator of p300) is directly targeted by the DNA damage signalling pathway where phosphorylation by ATM (ataxia telangiectasia mutated) kinase facilitates nuclear accumulation. Here, we show that Strap regulation reflects the coordinated interplay between different DNA damage-activated protein kinases, ATM and Chk2 (Checkpoint kinase 2), where phosphorylation by each kinase provides a distinct functional consequence on the activity of Strap. ATM phosphorylation prompts nuclear accumulation, which we show occurs by impeding nuclear export, whereas Chk2 phosphorylation augments protein stability once Strap has attained a nuclear location. These results highlight the various functional roles undertaken by the DNA damage signalling kinases in Strap control and, more generally, shed light on the pathways that contribute to the regulation of the p53 response.
Original languageEnglish
JournalEMBO Reports
ISSN1469-221X
DOIs
Publication statusPublished - 2008
Externally publishedYes

ID: 7750970