*nlm.life
			PubMed Journals: J Biol Chem

  Source:		PMID: 15632193


    		J Biol Chem. 2005 Mar 18;280(11):10264-76.
     		Epub 2005 Jan 4.

			SIRT1 deacetylation and repression of p300
			involves lysine residues 1020/1024 within
			the cell cycle regulatory domain 1.

			Bouras T(1), Fu M, Sauve AA, Wang F, Quong
			AA, Perkins ND, Hay RT, Gu W, Pestell RG.

			Author Information
			(1) Department of Oncology, Lombardi Comprehensive
			Cancer Center, Georgetown University, 3970
			Reservoir Rd.,Washington, DC 20057, USA.

			The SIR2 family of nicotinamide adenosine
			dinucleotide (NAD)-dependent deacetylases
			modulates diverse biological functions in
			different species, including longevity,
			apoptosis, cell cycle exit, and cellular
			differentiation. SIRT1, the closest mammalian
			ortholog of the yeast SIR2 (silent information
			regulator 2) gene, represses several transcription
			factors, including p53, NFkappaB and forkhead
			proteins. The p300 protein serves as a rate-limiting
			transcriptional cointegrator of diverse
			transcription factors either to activate
			or to repress transcription through modular
			subdomains. Herein, SIRT1 physically interacted
			with and repressed p300 transactivation,
			requiring the NAD-dependent deacetylase
			activity of SIRT1. SIRT1 repression involved
			the CRD1 transcriptional repression domain
			of p300. Two residues within the CRD1 domain
			(Lys-1020 and Lys-1024) were required for
			SIRT1 repression and served as substrates
			for SIRT1 deacetylation. These residues
			also serve as acceptor lysines for modification
			by the ubiquitin-like SUMO protein. The
			SUMO-specific protease SSP3 relieved SIRT1
			repression of p300. SSP3 antagonism of SIRT1
			required the SUMO-deconjugating function
			of SSP3. Thus, p300 serves as a deacetylase
			substrate for SIRT1 through a conserved
			SUMO consensus motif. Because p300 is a
			limiting transcriptional cofactor, deacetylation
			and repression of p300 by SIRT1 may serve
			an important integration point during metabolism
			and cellular differentiation.

			DOI: 10.1074/jbc.M408748200 PMID: 15632193
			[Indexed for MEDLINE]

     			                         Tweet       Print