Sirtuin 1 (SIRT1)

SIR2L1; Silent Mating Type Information Regulation 2 Homolog 1; NAD-Dependent Deacetylase Sirtuin-1; SIR2-like protein 1; SirtT1 75 kDa fragment

SPN	R887
HGNC	14929
MGI	2135607
PubMed	10381378
RGD	1308542
UniProt	Q96EB6
Wiki	Sirtuin_1

Sirtuin 1 is a member of the sirtuin family of proteins, homologs of the Sir2 gene in S. cerevisiae. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family.

Sirtuin 1 is downregulated in cells that have high insulin resistance and inducing its expression increases insulin sensitivity, suggesting the molecule is associated with improving insulin sensitivity.

Reference

"Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity."
Biochem. Biophys. Res. Commun. 260:273-279(1999) [PubMed] [Europe PMC] [Abstract]

"Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1 and HEY2 and is involved in HES1- and HEY2-mediated transcriptional repression."
Biochem. Biophys. Res. Commun. 301:250-257(2003) [PubMed] [Europe PMC] [Abstract]

"The DNA sequence and comparative analysis of human chromosome 10."
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase."
Cell 107:149-159(2001) [PubMed] [Europe PMC] [Abstract]

"Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence."
EMBO J. 21:2383-2396(2002) [PubMed] [Europe PMC] [Abstract]

"Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1."
J. Biol. Chem. 277:45099-45107(2002) [PubMed] [Europe PMC] [Abstract]

"Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan."
Nature 425:191-196(2003) [PubMed] [Europe PMC] [Abstract]

"Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase."
EMBO J. 23:2369-2380(2004) [PubMed] [Europe PMC] [Abstract]

"Mammalian SIRT1 represses forkhead transcription factors."
Cell 116:551-563(2004) [PubMed] [Europe PMC] [Abstract]

"FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1)."
J. Biol. Chem. 279:28873-28879(2004) [PubMed] [Europe PMC] [Abstract]

"Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin."
Mol. Cell 16:93-105(2004) [PubMed] [Europe PMC] [Abstract]

"Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase."
Science 303:2011-2015(2004) [PubMed] [Europe PMC] [Abstract]

"Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase."
Science 305:390-392(2004) [PubMed] [Europe PMC] [Abstract]

"Suppression of FOXO1 activity by FHL2 through SIRT1-mediated deacetylation."
EMBO J. 24:1021-1032(2005) [PubMed] [Europe PMC] [Abstract]

"Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins."
Mol. Biol. Cell 16:4623-4635(2005) [PubMed] [Europe PMC] [Abstract]

"Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications."
Mol. Cell. Biol. 25:8456-8464(2005) [PubMed] [Europe PMC] [Abstract]

"SIRT1 regulates HIV transcription via Tat deacetylation."
PLoS Biol. 3:210-220(2005) [PubMed] [Europe PMC] [Abstract]

"Composition and histone substrates of polycomb repressive group complexes change during cellular differentiation."
Proc. Natl. Acad. Sci. U.S.A. 102:1859-1864(2005) [PubMed] [Europe PMC] [Abstract]

"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]

"Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage."
Nat. Cell Biol. 8:1025-1031(2006) [PubMed] [Europe PMC] [Abstract]

"Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1."
Biochem. J. 407:451-460(2007) [PubMed] [Europe PMC] [Abstract]

"Sirt1 interacts with transducin-like enhancer of split-1 to inhibit nuclear factor kappaB-mediated transcription."
Biochem. J. 408:105-111(2007) [PubMed] [Europe PMC] [Abstract]

"Distinct C/EBPalpha motifs regulate lipogenic and gluconeogenic gene expression in vivo."
EMBO J. 26:1081-1093(2007) [PubMed] [Europe PMC] [Abstract]

"SIRT1 promotes DNA repair activity and deacetylation of Ku70."
Exp. Mol. Med. 39:8-13(2007) [PubMed] [Europe PMC] [Abstract]

"SIRT1 interacts with p73 and suppresses p73-dependent transcriptional activity."
J. Cell. Physiol. 210:161-166(2007) [PubMed] [Europe PMC] [Abstract]

"Sirtuin 1 is required for antagonist-induced transcriptional repression of androgen-responsive genes by the androgen receptor."
Mol. Endocrinol. 21:1807-1821(2007) [PubMed] [Europe PMC] [Abstract]

"Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity."
Mol. Cell 28:277-290(2007) [PubMed] [Europe PMC] [Abstract]

Erratum
Mol. Cell 28:513-513(2007)

"SIRT1 deacetylates and positively regulates the nuclear receptor LXR."
Mol. Cell 28:91-106(2007) [PubMed] [Europe PMC] [Abstract]

"SIRT1 regulates the function of the Nijmegen breakage syndrome protein."
Mol. Cell 27:149-162(2007) [PubMed] [Europe PMC] [Abstract]

"An acetylation/deacetylation-SUMOylation switch through a phylogenetically conserved psiKXEP motif in the tumor suppressor HIC1 regulates transcriptional repression activity."
Mol. Cell. Biol. 27:2661-2675(2007) [PubMed] [Europe PMC] [Abstract]

"SIRT1 regulates the histone methyl-transferase SUV39H1 during heterochromatin formation."
Nature 450:440-444(2007) [PubMed] [Europe PMC] [Abstract]

"SIRT1 regulates circadian clock gene expression through PER2 deacetylation."
Cell 134:317-328(2008) [PubMed] [Europe PMC] [Abstract]

"Epigenetic control of rDNA loci in response to intracellular energy status."
Cell 133:627-639(2008) [PubMed] [Europe PMC] [Abstract]

"JNK2-dependent regulation of SIRT1 protein stability."
Cell Cycle 7:3091-3097(2008) [PubMed] [Europe PMC] [Abstract]

"Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1 deacetylase and induces T cell hyperactivation."
Cell Host Microbe 3:158-167(2008) [PubMed] [Europe PMC] [Abstract]

"Regulation of WRN protein cellular localization and enzymatic activities by SIRT1-mediated deacetylation."
J. Biol. Chem. 283:7590-7598(2008) [PubMed] [Europe PMC] [Abstract]

"SIRT1 modulation of the acetylation status, cytosolic localization, and activity of LKB1. Possible role in AMP-activated protein kinase activation."
J. Biol. Chem. 283:27628-27635(2008) [PubMed] [Europe PMC] [Abstract]

"DBC1 is a negative regulator of SIRT1."
Nature 451:583-586(2008) [PubMed] [Europe PMC] [Abstract]

"Negative regulation of the deacetylase SIRT1 by DBC1."
Nature 451:587-590(2008) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation regulates SIRT1 function."
PLoS ONE 3:E4020-E4020(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy."
Proc. Natl. Acad. Sci. U.S.A. 105:3374-3379(2008) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"Carboxy-terminal phosphorylation of SIRT1 by protein kinase CK2."
Biochem. Biophys. Res. Commun. 381:372-377(2009) [PubMed] [Europe PMC] [Abstract]

"Investigating the ADP-ribosyltransferase activity of sirtuins with NAD analogues and 32P-NAD."
Biochemistry 48:2878-2890(2009) [PubMed] [Europe PMC] [Abstract]

"Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation."
Cell Metab. 9:327-338(2009) [PubMed] [Europe PMC] [Abstract]

"Transcriptional corepressor SMILE recruits SIRT1 to inhibit nuclear receptor estrogen receptor-related receptor gamma transactivation."
J. Biol. Chem. 284:28762-28774(2009) [PubMed] [Europe PMC] [Abstract]

"A c-Myc-SIRT1 feedback loop regulates cell growth and transformation."
J. Cell Biol. 185:203-211(2009) [PubMed] [Europe PMC] [Abstract]

"hSirT1-dependent regulation of the PCAF-E2F1-p73 apoptotic pathway in response to DNA damage."
Mol. Cell. Biol. 29:1989-1998(2009) [PubMed] [Europe PMC] [Abstract]

"JNK1 phosphorylates SIRT1 and promotes its enzymatic activity."
PLoS ONE 4:E8414-E8414(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]

"SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells."
Circ. Res. 106:1384-1393(2010) [PubMed] [Europe PMC] [Abstract]

"Role of SIRT1 in homologous recombination."
DNA Repair 9:383-393(2010) [PubMed] [Europe PMC] [Abstract]

"SIRT1 suppresses activator protein-1 transcriptional activity and cyclooxygenase-2 expression in macrophages."
J. Biol. Chem. 285:7097-7110(2010) [PubMed] [Europe PMC] [Abstract]

"SIRT1 regulates autoacetylation and histone acetyltransferase activity of TIP60."
J. Biol. Chem. 285:11458-11464(2010) [PubMed] [Europe PMC] [Abstract]

"SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic lipid metabolism."
J. Biol. Chem. 285:33959-33970(2010) [PubMed] [Europe PMC] [Abstract]

"Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha."
Mol. Cell 38:864-878(2010) [PubMed] [Europe PMC] [Abstract]

"SIRT1 regulates UV-induced DNA repair through deacetylating XPA."
Mol. Cell 39:247-258(2010) [PubMed] [Europe PMC] [Abstract]

"SIRT1 deacetylates APE1 and regulates cellular base excision repair."
Nucleic Acids Res. 38:832-845(2010) [PubMed] [Europe PMC] [Abstract]

"Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to inhibit LRH-1 transactivation."
Nucleic Acids Res. 38:4607-4619(2010) [PubMed] [Europe PMC] [Abstract]

"SIRT1 negatively regulates the mammalian target of rapamycin."
PLoS ONE 5:E9199-E9199(2010) [PubMed] [Europe PMC] [Abstract]

"SIRT1 undergoes alternative splicing in a novel auto-regulatory loop with p53."
PLoS ONE 5:E13502-E13502(2010) [PubMed] [Europe PMC] [Abstract]

"Regulation of global genome nucleotide excision repair by SIRT1 through xeroderma pigmentosum C."
Proc. Natl. Acad. Sci. U.S.A. 107:22623-22628(2010) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and HMGCS1,2."
Aging (Albany NY) 3:635-642(2011) [PubMed] [Europe PMC] [Abstract]

"Tumor necrosis factor alpha-mediated cleavage and inactivation of SirT1 in human osteoarthritic chondrocytes."
Arthritis Rheum. 63:2363-2373(2011) [PubMed] [Europe PMC] [Abstract]

"Regulation of unfolded protein response modulator XBP1s by acetylation and deacetylation."
Biochem. J. 433:245-252(2011) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"EVI1 up-regulates the stress responsive gene SIRT1 which triggers deacetylation and degradation of EVI1."
Biochim. Biophys. Acta 1809:269-275(2011) [PubMed] [Europe PMC] [Abstract]

"Energy sensing factors PGC-1alpha and SIRT1 modulate PXR expression and function."
Biochem. Pharmacol. 82:2008-2015(2011) [PubMed] [Europe PMC] [Abstract]

"Sirt1 deacetylates c-Myc and promotes c-Myc/Max association."
Int. J. Biochem. Cell Biol. 43:1573-1581(2011) [PubMed] [Europe PMC] [Abstract]

"MST1 promotes apoptosis through regulating Sirt1-dependent p53 deacetylation."
J. Biol. Chem. 286:6940-6945(2011) [PubMed] [Europe PMC] [Abstract]

"Cancer cell survival following DNA damage-mediated premature senescence is regulated by mammalian target of rapamycin (mTOR)-dependent Inhibition of sirtuin 1."
J. Biol. Chem. 286:19100-19108(2011) [PubMed] [Europe PMC] [Abstract]

"Stabilization of Suv39H1 by SirT1 is part of oxidative stress response and ensures genome protection."
Mol. Cell 42:210-223(2011) [PubMed] [Europe PMC] [Abstract]

"SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters its activities."
Mol. Cell. Biol. 31:4720-4734(2011) [PubMed] [Europe PMC] [Abstract]

"SIRT1 promotes N-Myc oncogenesis through a positive feedback loop involving the effects of MKP3 and ERK on N-Myc protein stability."
PLoS Genet. 7:E1002135-E1002135(2011) [PubMed] [Europe PMC] [Abstract]

"The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO."
PLoS Genet. 7:E1002235-E1002235(2011) [PubMed] [Europe PMC] [Abstract]

"Methyltransferase Set7/9 regulates p53 activity by interacting with Sirtuin 1 (SIRT1)."
Proc. Natl. Acad. Sci. U.S.A. 108:1925-1930(2011) [PubMed] [Europe PMC] [Abstract]

"The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy."
Sci. Signal. 4:RA46-RA46(2011) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"75kDa SirT1 blocks TNFalpha-mediated apoptosis in human osteoarthritic chondrocytes."
Arthritis Rheum. 64:718-728(2012) [PubMed] [Europe PMC] [Abstract]

"SIRT1 links CIITA deacetylation to MHC II activation."
Nucleic Acids Res. 39:9549-9558(2011) [PubMed] [Europe PMC] [Abstract]

"PML regulates PER2 nuclear localization and circadian function."
EMBO J. 31:1427-1439(2012) [PubMed] [Europe PMC] [Abstract]

"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]

"Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation."
Oncogene 31:1546-1557(2012) [PubMed] [Europe PMC] [Abstract]

"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]

"Deleted in breast cancer 1 (DBC1) deficiency results in apoptosis of breast cancer cells through impaired responses to UV-induced DNA damage."
Cancer Lett. 333:180-186(2013) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]