The p53 target Wig-1 regulates p53 mRNA stability through an AU-rich element

Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15756-61. doi: 10.1073/pnas.0900862106. Epub 2009 Sep 1.

Abstract

The p53 target gene Wig-1 encodes a double-stranded-RNA-binding zinc finger protein. We show here that Wig-1 binds to p53 mRNA and stabilizes it through an AU-rich element (ARE) in the 3' UTR of the p53 mRNA. This effect is mirrored by enhanced p53 protein levels in both unstressed cells and cells exposed to p53-activating stress agents. Thus, the p53 target Wig-1 is a previously undescribed ARE-regulating protein that acts as a positive feedback regulator of p53, with implications both for the steady-state levels of p53 and for the p53 stress response. Our data reveal a previously undescribed link between the tumor suppressor p53 and posttranscriptional gene regulation via AREs in mRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Animals
  • Base Composition
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Feedback, Physiological
  • Genes, p53
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • RNA Stability*
  • RNA, Messenger / chemistry
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism*
  • RNA, Small Interfering / genetics
  • RNA-Binding Proteins
  • Stress, Physiological
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • 3' Untranslated Regions
  • Carrier Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • ZMAT3 protein, human