Structural highlights
Function
[TTC5_MOUSE] Adapter protein involved in p53/TP53 response that acts by regulating and mediating the assembly of multi-protein complexes. Required to facilitate the interaction between JMY and p300/EP300 and increase p53/TP53-dependent transcription and apoptosis. Prevents p53/TP53 degradation by MDM2.[1] [2]
Publication Abstract from PubMed
Activation of p53 target genes for tumor suppression depends on the stress-specific regulation of transcriptional coactivator complexes. Strap (stress-responsive activator of p300) is activated upon DNA damage by ataxia telangiectasia mutated (ATM) and Chk2 kinases and is a key regulator of the p53 response. In addition to antagonizing Mdm2, Strap facilitates the recruitment of p53 coactivators, including JMY and p300. Strap is a predicted TPR-repeat protein, but shows only limited sequence identity with any protein of known structure. To address this and to elucidate the molecular mechanism of Strap activity we determined the crystal structure of the full-length protein at 2.05 A resolution. The structure of Strap reveals an atypical six tetratricopeptide repeat (TPR) protein that also contains an unexpected oligonucleotide/oligosaccharide-binding (OB)-fold domain. This previously unseen domain organization provides an extended superhelical scaffold allowing for protein-protein as well as protein-DNA interaction. We show that both of the TPR and OB-fold domains localize to the chromatin of p53 target genes and exhibit intrinsic regulatory activity necessary for the Strap-dependent p53 response.
The p53 cofactor Strap exhibits an unexpected TPR motif and oligonucleotide-binding (OB)-fold structure.,Adams CJ, Pike AC, Maniam S, Sharpe TD, Coutts AS, Knapp S, La Thangue NB, Bullock AN Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3778-83. Epub 2012 Feb 23. PMID:22362889[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Shikama N, Lee CW, France S, Delavaine L, Lyon J, Krstic-Demonacos M, La Thangue NB. A novel cofactor for p300 that regulates the p53 response. Mol Cell. 1999 Sep;4(3):365-76. PMID:10518217
- ↑ Demonacos C, Krstic-Demonacos M, Smith L, Xu D, O'Connor DP, Jansson M, La Thangue NB. A new effector pathway links ATM kinase with the DNA damage response. Nat Cell Biol. 2004 Oct;6(10):968-76. Epub 2004 Sep 19. PMID:15448695 doi:http://dx.doi.org/10.1038/ncb1170
- ↑ Adams CJ, Pike AC, Maniam S, Sharpe TD, Coutts AS, Knapp S, La Thangue NB, Bullock AN. The p53 cofactor Strap exhibits an unexpected TPR motif and oligonucleotide-binding (OB)-fold structure. Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):3778-83. Epub 2012 Feb 23. PMID:22362889 doi:10.1073/pnas.1113731109
