Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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 Å 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.

Original publication

DOI

10.1073/pnas.1113731109

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

06/03/2012

Volume

109

Pages

3778 - 3783

Keywords

Amino Acid Motifs, Animals, Carrier Proteins, Chromatin, Crystallography, X-Ray, DNA Damage, E1A-Associated p300 Protein, Genes, p53, Humans, Mice, Models, Molecular, Neoplasm Proteins, Oligonucleotides, Protein Binding, Protein Conformation, Protein Folding, Protein Structure, Tertiary, Tumor Suppressor Protein p53