Tags

Type your tag names separated by a space and hit enter

SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1.
J Biol Chem. 2005 Mar 18; 280(11):10264-76.JB

Abstract

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.

Authors+Show Affiliations

Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, 3970 Reservoir Rd.,Washington, DC 20057, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15632193

Citation

Bouras, Toula, et al. "SIRT1 Deacetylation and Repression of P300 Involves Lysine Residues 1020/1024 Within the Cell Cycle Regulatory Domain 1." The Journal of Biological Chemistry, vol. 280, no. 11, 2005, pp. 10264-76.
Bouras T, Fu M, Sauve AA, et al. SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. J Biol Chem. 2005;280(11):10264-76.
Bouras, T., Fu, M., Sauve, A. A., Wang, F., Quong, A. A., Perkins, N. D., Hay, R. T., Gu, W., & Pestell, R. G. (2005). SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. The Journal of Biological Chemistry, 280(11), 10264-76.
Bouras T, et al. SIRT1 Deacetylation and Repression of P300 Involves Lysine Residues 1020/1024 Within the Cell Cycle Regulatory Domain 1. J Biol Chem. 2005 Mar 18;280(11):10264-76. PubMed PMID: 15632193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. AU - Bouras,Toula, AU - Fu,Maofu, AU - Sauve,Anthony A, AU - Wang,Fang, AU - Quong,Andrew A, AU - Perkins,Neil D, AU - Hay,Ronald T, AU - Gu,Wei, AU - Pestell,Richard G, Y1 - 2005/01/04/ PY - 2005/1/6/pubmed PY - 2005/4/26/medline PY - 2005/1/6/entrez SP - 10264 EP - 76 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 280 IS - 11 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/15632193/SIRT1_deacetylation_and_repression_of_p300_involves_lysine_residues_1020/1024_within_the_cell_cycle_regulatory_domain_1_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=15632193 DB - PRIME DP - Unbound Medicine ER -