Signalling DNA damage by regulating p53 co-factor activity.
In response to DNA damage the related phosphatidylinositol-3-OH-kinase-like-kinases ATM and ATR phosphorylate downstream protein targets which facilitate the DNA damage response. A new pathway in which ATM phosphorylates the transcriptional co-factor Strap has been elucidated. Phosphorylation causes the stabilization of nuclear Strap and favours the formation of a stress-responsive co-activator complex. Strap activity enhances p53 acetylation, and augments the response to DNA damage. Most interestingly, in AT cells Strap remains cytoplasmic, and a mutant derivative that cannot be phosphorylated by ATM is similarly localised to the cytoplasm. These results argue that Strap is an important downstream effector in the DNA damage response.
Smith
Linda
L
Division of Biochemistry and Molecular Biology, University of Glasgow, Glasgow, Scotland, UK.
La Thangue
Nicholas B
NB
D000107:Acetylation; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C434146:Strap protein; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases