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The Stress-responsive activator of p300 (Strap) is a transcription co-factor that has an important role in the control of DNA damage response through its ability to regulate p53 activity. Recent studies have however suggested that Strap takes on a wider role in regulating the cellular response to stress. Thus, Strap is now known to be inducible by heat shock and stimulate the transcription of heat-shock genes. A chromatin-associated complex involving heat-shock factor 1 (HSF1), Strap and the p300 co-activator assembles on the HSP70 gene promoter, and Strap augments HSF1 binding and chromatin acetylation in HSP genes, most probably through recruiting p300 acetyltransferase. Cells depleted of Strap do not survive under heat-shock conditions. It appears therefore that Strap is an essential co-factor that acts at the level of chromatin control to regulate heat-shock-responsive transcription. These recent studies underscore the central role taken on by transcription co-factors in integrating and co-ordinating different cellular stress response pathways.

The Stress-responsive activator of p300 (Strap) is a transcription cofactor that has an important role in the control of DNA damage response through its ability to regulate p53 activity. Here, we report that Strap is inducible by heat shock and stimulates the transcription of heat-shock genes. A chromatin-associated complex involving heat-shock factor 1 (HSF1), Strap and the p300 coactivator assembles on the heat-shock protein 70 (hsp70) promoter, and Strap augments HSF1 binding and chromatin acetylation in Hsp genes, most probably through the p300 histone acetyltransferase. Cells depleted of Strap do not survive under heat-shock conditions. These results indicate that Strap is an essential cofactor that acts at the level of chromatin control to regulate heat-shock-responsive transcription.

The related kinases ATM (ataxia-telangiectasia mutated) and ATR (ataxia-telangiectasia and Rad3-related) phosphorylate a limited number of downstream protein targets in response to DNA damage. Here we report a new pathway in which ATM kinase signals the DNA damage response by targeting the transcriptional cofactor Strap. ATM phosphorylates Strap at a serine residue, stabilizing nuclear Strap and facilitating formation of a stress-responsive co-activator complex. Strap activity enhances p53 acetylation, and augments the response to DNA damage. Strap remains localized in the cytoplasm in cells derived from ataxia telangiectasia individuals with defective ATM, as well as in cells expressing a Strap mutant that cannot be phosphorylated by ATM. Targeting Strap to the nucleus reinstates protein stabilization and activates the DNA damage response. These results indicate that the nuclear accumulation of Strap is a critical regulator in the damage response, and argue that this function can be assigned to ATM through the DNA damage-dependent phosphorylation of Strap. [ABSTRACT FROM AUTHOR]