Hydrogen peroxide induces p16 INK4a through an AUF1‐dependent manner

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.