hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase

Homayoun Vaziri, Scott K. Dessain, Elinor Ng Eaton, Shin Ichiro Imai, Roy A. Frye, Tej K. Pandita, Leonard Guarente, Robert A. Weinberg

Research output: Contribution to journalArticlepeer-review

2157 Scopus citations

Abstract

DNA damage-induced acetylation of p53 protein leads to its activation and either growth arrest or apoptosis. We show here that the protein product of the gene hSIR2 , the human homolog of the S. cerevisiae Sir2 protein known to be involved in cell aging and in the response to DNA damage, binds and deacetylates the p53 protein with a specificity for its C-terminal Lys382 residue, modification of which has been implicated in the activation of p53 as a transcription factor. Expression of wild-type hSir2 in human cells reduces the transcriptional activity of p53. In contrast, expression of a catalytically inactive hSir2 protein potentiates p53-dependent apoptosis and radiosensitivity. We propose that hSir2 is involved in the regulation of p53 function via deacetylation.

Original languageEnglish (US)
Pages (from-to)149-159
Number of pages11
JournalCell
Volume107
Issue number2
DOIs
StatePublished - Oct 19 2001

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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