@article{562679faad59447d847a3919ba6e94e7,
title = "hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase",
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.",
author = "Homayoun Vaziri and Dessain, {Scott K.} and Eaton, {Elinor Ng} and Imai, {Shin Ichiro} and Frye, {Roy A.} and Pandita, {Tej K.} and Leonard Guarente and Weinberg, {Robert A.}",
note = "Funding Information: We are grateful to Dr. Ettore Appella for providing us with anti-acetylated p53 antibodies and acetylation mutant p53 constructs. We thank Sam Benchimol for critical comments, Steven Johnston for help with bioinformatics, and Richard Cook for help with the peptide analysis. We also thank the Weinberg Lab for helpful discussions. This work was supported by NIH/NCI grant R01 CA78461 to R.A.W., NIH NS34746 to T.K.P., NIH and Ellison Medical Foundation grants to L.G. and by an NHLBI/NIH fellowship to S.K.D., K08 HL04463. The majority of this work was accomplished while support to H.V. was kindly given by the Human Frontier Science Organization. We also thank the Jos{\'e} Carreras International Leukemia Foundation for fellowship support to HV.",
year = "2001",
month = oct,
day = "19",
doi = "10.1016/S0092-8674(01)00527-X",
language = "English (US)",
volume = "107",
pages = "149--159",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",
}