Hydrogen peroxide induces p16INK4a through an AUF1-dependent manner

✍ Scribed by Gai E Guo; Li Wei Ma; Bin Jiang; Jie Yi; Tan Jun Tong; Wen Gong Wang

• Book ID: 102302325
• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 342 KB
• Volume: 109
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.22474

✦ Synopsis

Abstract

Elevation of p16^INK4a^ has been described as an important mechanism for hydrogen peroxide (H~2~O~2~)‐induced replicative senescence. However, the mechanisms underlying remain unknown. In this study, we demonstrate an important role of RNA‐binding protein AUF1‐mediated mRNA turnover in H~2~O~2~‐induced p16^INK4a^ expression. The induction of p16 by H~2~O~2~ was accompanied with declined cytoplasmic AUF1 level. Accordingly, exposure of cells to H~2~O~2~ remarkably reduced the binding of AUF1 to p16 3′UTR and increased the half‐life of an EGFP‐p16‐3′UTR chimeric transcript. In AUF1‐silenced cells, the effect of H~2~O~2~ on p16 induction was abolished. Furthermore, in cells co‐transfected with vectors expressing AUF1s, treatment with H~2~O~2~ failed to significantly reduce the expression of AUF1 and subsequently elevate the levels of p16. Moreover, HeLa cells overexpressing AUF1s were resistant to H~2~O~2~‐induced senescence. Our results indicate that AUF1 is critical for H~2~O~2~‐induced p16 expression and cellular senescence. J. Cell. Biochem. 109: 1000–1005, 2010. © 2010 Wiley‐Liss, Inc.