Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence
Language: 
English
Abstract: 

The yeast Sir2 protein mediates chromatin silencing through an intrinsic NAD-dependent histone deacetylase activity. Sir2 is a conserved protein and was recently shown to regulate lifespan extension both in budding yeast and worms. Here, we show that SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells upon overexpression of either PML or oncogenic Ras (Ha-rasV12). SIRT1 binds and deacetylates p53, a component of PML nuclear bodies, and it can repress p53-mediated transactivation. Moreover, we show that SIRT1 and p53 co-localize in nuclear bodies upon PML upregulation. When overexpressed in primary mouse embryo fibroblasts (MEFs), SIRT1 antagonizes PML-induced acetylation of p53 and rescues PML-mediated premature cellular senescence. Taken together, our data establish the SIRT1 deacetylase as a novel negative regulator of p53 function capable of modulating cellular senescence.

Author(s): 
Langley, Emma
Pearson, Mark
Faretta, Mario
Bauer, Uta-Maria
Frye, Roy A.
Minucci, Saverio
Pelicci, Pier Giuseppe
Kouzarides, Tony
Item Type: 
Journal Article
Publication Title: 
The EMBO journal
Journal Abbreviation: 
EMBO J.
Publication Date: 
5/15/2002
Publication Year: 
2002
Pages: 
2383-2396
Volume: 
21
Issue: 
10
ISSN: 
0261-4189
DOI: 
10.1093/emboj/21.10.2383
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 12006491 PMCID: PMC126010

Turabian/Chicago Citation

Emma Langley, Mark Pearson, Mario Faretta, Uta-Maria Bauer, Roy A. Frye, Saverio Minucci, Pier Giuseppe Pelicci and Tony Kouzarides. 5/15/2002. "Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence." The EMBO journal 21: 10: 2383-2396. 10.1093/emboj/21.10.2383.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1093/emboj/21.10.2383 | issn = 0261-4189 | volume = 21 | pages = 2383-2396 | last = Langley | first = Emma | coauthors = Pearson, Mark, Faretta, Mario, Bauer, Uta-Maria, Frye, Roy A., Minucci, Saverio, Pelicci, Pier Giuseppe, Kouzarides, Tony | title = Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence | journal = The EMBO journal | date = 5/15/2002 | pmid = | pmc = }} </ref>