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, Zhi Xiong Jim Xiao

    Research output: Contribution to journalArticlepeer-review

    320 Citations (Scopus)

    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 isomerase4-9. 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 Pin 1. 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.

    Original languageEnglish
    Pages (from-to)849-853
    Number of pages5
    JournalNature
    Volume419
    Issue number6909
    DOIs
    Publication statusPublished - 2002 Oct 24

    ASJC Scopus subject areas

    • General

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