- Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene. [1] [2] [3] SIRT1 stands for sirtuin (silent ...
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SIRT1 sirtuin 1 Also known as: SIR2L1 Summary. This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the ...- Sirtuin or Sir2 proteins are a class of proteins that possess either mono-ADP-ribosyltransferase, or deacylase activity, including deacetylase, desuccinylase ...
Sirtuin 1
From Wikipedia, the free encyclopedia
Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene.[1][2][3]Sirtuin 1 Available structures PDB Ortholog search: PDBe, RCSB [show]List of PDB id codes Identifiers Symbols SIRT1 ; SIR2; SIR2L1; hSIR2 External IDs OMIM: 604479 MGI: 2135607 HomoloGene: 56556 ChEMBL: 4506 GeneCards: SIRT1 Gene [show]Gene ontology RNA expression pattern 
More reference expression data Orthologs Species Human Mouse Entrez 23411 93759 Ensembl ENSG00000096717 ENSMUSG00000020063 UniProt Q96EB6 Q923E4 RefSeq (mRNA) NM_001142498 NM_001159589 RefSeq (protein) NP_001135970 NP_001153061 Location (UCSC) Chr 10:
67.88 – 67.92 MbChr 10:
63.32 – 63.38 MbPubMed search [1] [2]
SIRT1 stands for sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae), referring to the fact that its sirtuin homolog (biological equivalent across species) in yeast (S. cerevisiae) is Sir2. SIRT1 is an enzyme that deacetylates proteins that contribute to cellular regulation (reaction to stressors, longevity).[4]
Contents
Function
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.[2]
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.[5] Furthermore, SIRT1 was shown to de-acetylate and affect the activity of both members of the PGC1-alpha/ERR-alpha complex, which are essential metabolic regulatory transcription factors.[6][7][8][9][10][11]
Selective ligands
Activators
- Lamin A is a protein that had been identified as a direct activator of Sirtuin 1 during a study on Progeria.[12]
- Resveratrol has been claimed to be an activator of Sirtuin 1,[13] but this effect has been disputed based on the fact that the initially used activity assay, using a non-physiological substrate peptide, can produce artificial results.[14][15] Resveratrol increases the expression of SIRT1, meaning that it does increase the activity of SIRT1, though not necessarily by direct activation.[5] However, resveratrol was later shown to directly activate Sirtuin 1 against non-modified peptide substrates.[16][17] Resveratrol also enhances the binding between Sirtuin 1 and Lamin A.[12]
- SRT-1720 was also claimed to be an activator,[13] but this now has been questioned.[18]
Interactions
Sirtuin 1 has been shown to interact with HEY2,[19] PGC1-alpha,[8] and ERR-alpha.[6] Mir-132 microRNA has been reported to interact with Sirtuin 1 mRNA, so as to reduce protein expression. This has been linked to insulin resistance in the obese.[20]
Human Sirt1 has been reported having 136 direct interactions in Interactomic studies involved in numerous processes.[21]
References
- Frye RA (June 1999). "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 (1): 273–9. doi:10.1006/bbrc.1999.0897. PMID 10381378.
- Sharma A, Gautam V, Costantini S, Paladino A, Colonna G (2012). "Interactomic and pharmacological insights on human sirt-1". Front Pharmacol 3: 40. doi:10.3389/fphar.2012.00040. PMC 3311038. PMID 22470339.
Further reading
- Frye RA (1999). "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 (1): 273–9. doi:10.1006/bbrc.1999.0897. PMID 10381378.
- Frye RA (2000). "Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins". Biochem. Biophys. Res. Commun. 273 (2): 793–8. doi:10.1006/bbrc.2000.3000. PMID 10873683.
- Wiemann S, Weil B, Wellenreuther R, Gassenhuber J, Glassl S, Ansorge W, Böcher M, Blöcker H, Bauersachs S, Blum H, Lauber J, Düsterhöft A, Beyer A, Köhrer K, Strack N, Mewes HW, Ottenwälder B, Obermaier B, Tampe J, Heubner D, Wambutt R, Korn B, Klein M, Poustka A (2001). "Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs". Genome Res. 11 (3): 422–35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166.
- Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W (2001). "Negative control of p53 by Sir2alpha promotes cell survival under stress". Cell 107 (2): 137–48. doi:10.1016/S0092-8674(01)00524-4. PMID 11672522.
- Vaziri H, Dessain SK, Ng Eaton E, Imai SI, Frye RA, Pandita TK, Guarente L, Weinberg RA (2001). "hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase". Cell 107 (2): 149–59. doi:10.1016/S0092-8674(01)00527-X. PMID 11672523.
- Langley E, Pearson M, Faretta M, Bauer UM, Frye RA, Minucci S, Pelicci PG, Kouzarides T (2002). "Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence". EMBO J. 21 (10): 2383–96. doi:10.1093/emboj/21.10.2383. PMC 126010. PMID 12006491.
- Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA (2002). "Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1". J. Biol. Chem. 277 (47): 45099–107. doi:10.1074/jbc.M205670200. PMID 12297502.
- Travers H, Spotswood HT, Moss PA, Turner BM (2002). "Human CD34+ hematopoietic progenitor cells hyperacetylate core histones in response to sodium butyrate, but not trichostatin A". Exp. Cell Res. 280 (2): 149–58. doi:10.1006/excr.2002.5632. PMID 12413881.
- Takata T, Ishikawa F (2003). "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 (1): 250–7. doi:10.1016/S0006-291X(02)03020-6. PMID 12535671.
- Senawong T, Peterson VJ, Avram D, Shepherd DM, Frye RA, Minucci S, Leid M (2003). "Involvement of the histone deacetylase SIRT1 in chicken ovalbumin upstream promoter transcription factor (COUP-TF)-interacting protein 2-mediated transcriptional repression". J. Biol. Chem. 278 (44): 43041–50. doi:10.1074/jbc.M307477200. PMC 2819354. PMID 12930829.
- Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003). "Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan". Nature 425 (6954): 191–6. doi:10.1038/nature01960. PMID 12939617.
- Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME (2004). "Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase". Science 303 (5666): 2011–5. doi:10.1126/science.1094637. PMID 14976264.
- Motta MC, Divecha N, Lemieux M, Kamel C, Chen D, Gu W, Bultsma Y, McBurney M, Guarente L (2004). "Mammalian SIRT1 represses forkhead transcription factors". Cell 116 (4): 551–63. doi:10.1016/S0092-8674(04)00126-6. PMID 14980222.
- van der Horst A, Tertoolen LG, de Vries-Smits LM, Frye RA, Medema RH, Burgering BM (2004). "FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity protein hSir2(SIRT1)". J. Biol. Chem. 279 (28): 28873–9. doi:10.1074/jbc.M401138200. PMID 15126506.
- Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW (2004). "Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase". EMBO J. 23 (12): 2369–80. doi:10.1038/sj.emboj.7600244. PMC 423286. PMID 15152190.
- Picard F, Kurtev M, Chung N, Topark-Ngarm A, Senawong T, Machado De Oliveira R, Leid M, McBurney MW, Guarente L (2004). "Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma". Nature 429 (6993): 771–6. doi:10.1038/nature02583. PMC 2820247. PMID 15175761.
- Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA (2004). "Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase". Science 305 (5682): 390–2. doi:10.1126/science.1099196. PMID 15205477.
External links
- Corante weblog by Derek Lowe about sir2 and SIRT1 research.
- SIRT1 human gene location in the UCSC Genome Browser.
- SIRT1 human gene details in the UCSC Genome Browser.
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Sirtuin 1 - Wikipedia, the free encyclopedia
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