The prolyl isomerase Pin1 is a regulator of p53 in genotoxic response

Hongwu Zheng, Han You, Xiao Zhen Zhou, Stephen A. Murray, Takafumi Uchida, Gerburg Wulf, Ling Gu, Xiaoren Tang, Kun Ping Lu and Zhi-Xiong Jim Xiao ()
Additional contact information
Hongwu Zheng: Boston University School of Medicine
Han You: Boston University School of Medicine
Xiao Zhen Zhou: Beth Israel Deaconess Medical Center, Harvard Medical School
Stephen A. Murray: Boston University School of Medicine
Takafumi Uchida: Institute of Development, Aging and Cancer, Tohoku University
Gerburg Wulf: Beth Israel Deaconess Medical Center, Harvard Medical School
Ling Gu: Boston University School of Medicine
Xiaoren Tang: Boston University School of Medicine
Kun Ping Lu: Beth Israel Deaconess Medical Center, Harvard Medical School
Zhi-Xiong Jim Xiao: Boston University School of Medicine

Nature, 2002, vol. 419, issue 6909, 849-853

Abstract: Abstract p53 is activated in response to various genotoxic stresses resulting in cell cycle arrest or apoptosis1,2. It is well documented that DNA damage leads to phosphorylation and activation of p53 (refs 1–3), yet how p53 is activated is still not fully understood. Here we report that DNA damage specifically induces p53 phosphorylation on Ser/Thr-Pro motifs, which facilitates its interaction with Pin1, a member of peptidyl-prolyl isomerase4,5,6,7,8,9. Furthermore, the interaction of Pin1 with p53 is dependent on the phosphorylation that is induced by DNA damage. Consequently, Pin1 stimulates the DNA-binding activity and transactivation function of p53. The Pin1-mediated p53 activation requires the WW domain, a phosphorylated Ser/Thr-Pro motif interaction module, and the isomerase activity of Pin1. Moreover, Pin1-deficient cells are defective in p53 activation and timely accumulation of p53 protein, and exhibit an impaired checkpoint control in response to DNA damage. Together, these data suggest a mechanism for p53 regulation in cellular response to genotoxic stress.

Date: 2002
References: Add references at CitEc
Citations: View citations in EconPapers (3)

Downloads: (external link)
https://www.nature.com/articles/nature01116 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:419:y:2002:i:6909:d:10.1038_nature01116

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01116

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().