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Acetylate to kill or save

More p53 (green) is cytoplasmic when K320 is acetylated (bottom).

Mammalian p53 can kill, or it can save. The end result, according to Knights et al. (page 533), depends on opposing acetylation events that send p53 down disparate paths.

The stabilization of p53 following cellular damage can trigger either apoptosis or a reversible cell cycle checkpoint that probably gives cells time to recover. As either savior or killer, p53 is subject to a battery of posttranslational modifications, including phosphorylation and acetylation. One such acetylation event (on K373) is now shown to trigger apoptosis, whereas another (on K320) works against death.

To understand how, the authors expressed mutant versions of p53 that mimic the acetylation events. After a brief treatment with a mild DNA-damaging agent, only cells with K320-modified p53 resumed proliferation; the rest died. The promoters bound, and genes activated, by the two p53 mimics correlated with their outcomes.

Many proapoptotic genes have promoters that might be too low in affinity for K320-acetylated p53. This form of p53 was in a slightly denatured state with less intrinsic DNA-binding ability. It was also more readily exported from the nucleus due to a block in serine-15 phosphorylation.

The K320 site is not conserved in fly and worm p53, which are solely death-inducing proteins. Mammalian tissues lacking regenerative abilities might have evolved the survival effect as a way to help maintain their numbers. Indeed, the group recently found that only K320 is acetylated during the neuronal maturation and neurite outgrowth that accompany regeneration.

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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Related Article

Distinct p53 acetylation cassettes differentially influence gene-expression patterns and cell fate

Chad D. Knights, Jason Catania, Simone Di Giovanni, Selen Muratoglu, Ricardo Perez, Amber Swartzbeck, Andrew A. Quong, Xiaojing Zhang, Terry Beerman, Richard G. Pestell, and Maria Laura Avantaggiati
J. Cell Biol. 2006 173: 533-544. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 761K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Related Collections Related Article Social Bookmarking                            What's this?