Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis - PubMed (original) (raw)

Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis

Yi Tang et al. Mol Cell. 2006.

Free article

Abstract

Upon DNA damage and other types of stress, p53 induces either cell-cycle arrest or apoptosis depending on the cellular context. However, the molecular mechanisms that govern the choice between cell-cycle arrest and apoptosis are not well understood. Here, we show that Tip60 is required for both cell growth arrest and apoptosis mediated by p53 and also induces its acetylation specifically at lysine 120 (K120) within the DNA-binding domain. Interestingly, this modification is crucial for p53-dependent apoptosis but is dispensable for its mediated growth arrest. K120 is a recurrent site for p53 mutation in human cancer, and the corresponding acetylation-defective tumor mutant (K120R) abrogates p53-mediated apoptosis, but not growth arrest. Thus, our study demonstrates that Tip60-dependent acetylation of p53 at K120 modulates the decision between cell-cycle arrest and apoptosis, and it reveals that the DNA-binding core domain is an important target for p53 regulation by posttranslational modifications.

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Comment in

To die or not to die: a HAT trick.
Tyteca S, Legube G, Trouche D. Tyteca S, et al. Mol Cell. 2006 Dec 28;24(6):807-8. doi: 10.1016/j.molcel.2006.12.005. Mol Cell. 2006. PMID: 17189182 Review.

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Tip60-dependent acetylation of p53 modulates the decision between cell-cycle arrest and apoptosis - PubMed (original) (raw)