ATM and Chk2 kinase target the p53 cofactor Strap.

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

doi:10.1038/embor.2008.186

ATM and Chk2 kinase target the p53 cofactor Strap.

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

17 Citations (Scopus)

Abstract

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 language	English
Journal	EMBO Reports
ISSN	1469-221X
DOIs	https://doi.org/10.1038/embor.2008.186
Publication status	Published - 2008
Externally published	Yes

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title = "ATM and Chk2 kinase target the p53 cofactor Strap.",

abstract = "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.",

author = "Adams, {Cassandra J} and Graham, {Anne L} and Martin Jansson and Coutts, {Amanda S} and Mariola Edelmann and Linda Smith and Benedikt Kessler and {La Thangue}, {Nicholas B}",

year = "2008",

doi = "10.1038/embor.2008.186",

language = "English",

journal = "E M B O Reports",

issn = "1469-221X",

publisher = "Wiley-Blackwell",

}

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T1 - ATM and Chk2 kinase target the p53 cofactor Strap.

AU - Adams, Cassandra J

AU - Graham, Anne L

AU - Jansson, Martin

AU - Coutts, Amanda S

AU - Edelmann, Mariola

AU - Smith, Linda

AU - Kessler, Benedikt

AU - La Thangue, Nicholas B

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

U2 - 10.1038/embor.2008.186

DO - 10.1038/embor.2008.186

M3 - Journal article

C2 - 18833288

SN - 1469-221X

JO - E M B O Reports

JF - E M B O Reports

ER -

ATM and Chk2 kinase target the p53 cofactor Strap.

Abstract

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