The p53 cofactor Strap exhibits an unexpected TPR motif and oligonucleotide-binding (OB)-fold structure.

Proceedings of the National Academy of Sciences of the United States of America
Cassandra J AdamsAlex N Bullock

Abstract

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.

References

Oct 13, 1999·Molecular Cell·N ShikamaN B La Thangue
Aug 21, 2001·Molecular Cell·C DemonacosN B La Thangue
Dec 31, 2002·Current Opinion in Structural Biology·Vickery Arcus
Jan 28, 2003·Nature Structural Biology·Ryan J FletcherXiaojiang S Chen
Dec 9, 2003·Trends in Biochemical Sciences·Luca D D'Andrea, Lynne Regan
Sep 1, 1994·Acta Crystallographica. Section D, Biological Crystallography·UNKNOWN Collaborative Computational Project, Number 4
May 1, 1997·Acta Crystallographica. Section D, Biological Crystallography·G N MurshudovE J Dodson
Sep 28, 2004·Nature Cell Biology·Constantinos DemonacosNicholas B La Thangue
May 4, 2005·Biochemical and Biophysical Research Communications·Amanda S Coutts, Nicholas B La Thangue
Dec 22, 2005·Acta Crystallographica. Section D, Biological Crystallography·Andrew G W Leslie
Dec 22, 2005·Acta Crystallographica. Section D, Biological Crystallography·Philip Evans
Feb 4, 2006·Molecular Cell·Christopher L Brooks, Wei Gu
Feb 17, 2006·The EMBO Journal·Alasdair H MiltonNicholas B La Thangue
Dec 25, 2007·Acta Crystallographica. Section A, Foundations of Crystallography·George M Sheldrick
Jan 19, 2008·EMBO Reports·L Panagiotis ZalmasNicholas B La Thangue
May 3, 2008·EMBO Reports·Danmei XuNicholas B La Thangue
Aug 23, 2008·Nature Reviews. Molecular Cell Biology·Fiona Murray-ZmijewskiXin Lu
Oct 4, 2008·EMBO Reports·Cassandra J AdamsNicholas B La Thangue
Nov 18, 2008·Nature Cell Biology·Martin JanssonNicholas B La Thangue
May 5, 2009·Cell·Karen H Vousden, Carol Prives
Aug 12, 2009·Nature Structural & Molecular Biology·Jing WangBrenda A Schulman
Sep 25, 2009·Nature Reviews. Cancer·Arnold J Levine, Moshe Oren
Nov 10, 2009·Proceedings of the National Academy of Sciences of the United States of America·Amanda S CouttsNicholas B La Thangue
Nov 26, 2009·Nature Reviews. Cancer·Christopher J BrownDavid P Lane
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
May 12, 2010·Nucleic Acids Research·Liisa Holm, Päivi Rosenström
Jun 3, 2010·Critical Reviews in Biochemistry and Molecular Biology·Rachel Litman Flynn, Lee Zou
Dec 15, 2010·Molecular Endocrinology·Laura DaviesMarija Krstic-Demonacos

❮ Previous
Next ❯

Citations

Aug 8, 2012·Acta Crystallographica. Section D, Biological Crystallography·Jeffrey A BellRamy Farid
Apr 4, 2013·BMC Molecular Biology·Nicholas W AshtonDerek J Richard
Aug 30, 2014·Cell Death and Differentiation·S ManiamN B La Thangue
Jun 21, 2017·Molecular and Cellular Biology·Huda H Al-KhalafAbdelilah Aboussekhra
Nov 16, 2019·Science·Zhewang LinRamanujan S Hegde
May 23, 2020·Journal of Medical Genetics·Arisha RasheedAshleigh Schaffer
Oct 19, 2017·Scientific Reports·Oliviero CarugoDavide M Proserpio
Jun 26, 2021·Journal of Human Genetics·Sachiko MiyamotoHirotomo Saitsu

❮ Previous
Next ❯

Related Concepts

Related Feeds

Ataxia telangiectasia (MDS)

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.

Ataxia telangiectasia

Ataxia telangiectasia is a rare neurodegenerative diseases caused by defects in the ATM gene, which is involved in DNA damage recognition and repair pathways. Here is the latest research on this autosomal recessive disease.