SIRT6

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Sirtuin 6
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols SIRT6 ; SIR2L6
External IDs OMIM606211 MGI1354161 HomoloGene6924 GeneCards: SIRT6 Gene
EC number 2.4.2.31
RNA expression pattern
PBB GE SIRT6 219613 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 51548 50721
Ensembl ENSG00000077463 ENSMUSG00000034748
UniProt Q8N6T7 P59941
RefSeq (mRNA) NM_001193285 NM_001163430
RefSeq (protein) NP_001180214 NP_001156902
Location (UCSC) Chr 19:
4.17 – 4.18 Mb
Chr 10:
81.62 – 81.63 Mb
PubMed search [1] [2]

Sirtuin-6 (SIRT6) is a stress responsive protein deacetylase and mono-ADP ribosyltransferase enzyme encoded by the SIRT6 gene.[1][2] SIRT6 functions in multiple molecular pathways related to aging, including DNA repair, telomere maintenance, glycolysis and inflammation.[1]

Function[edit]

Studies in mice have revealed that Sirt6 is essential for post-natal development and survival. Sirt6 knock-out mice, in which the gene encoding Sirt6 has been disrupted, exhibit a severe progeria, or premature aging syndrome, characterized by spinal curvature, greying of the fur, lymphopenia and low levels of blood glucose.[3] The lifespan of Sirt6 knock-out mice is typically one to three months, dependent upon the strain in which the Sirt6 gene has been deleted. By contrast, wild type mice, which retain expression of Sirt6, exhibit a maximum lifespan of two to four years.[3]

Mice which have been genetically engineered to overexpress, or produce more, Sirt6 protein exhibit an extended maximum lifespan. This lifespan extension, of about 15-16 percent, is observed only in male mice.[4]

Clinical relevance[edit]

The medical and therapeutic relevance of SIRT6 in humans remains unclear. SIRT6 may be an attractive drug target for pharmocological activation in several diseases.[5] Because SIRT6 attenuates glycolysis and inflammation, the gene is of medical interest in the context of several diseases, including diabetes and arthritis.[6] Additionally, SIRT6 may be relevant in the context of cancer. Several studies have indicated that SIRT6 is selectively inactivated during oncogenesis in a variety of tumor types; a separate study demonstrated that SIRT6 overexpression was selectively cytotoxic to cancer cells.[7]

References[edit]

  1. ^ a b Frye RA (Aug 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. 
  2. ^ "Entrez Gene: SIRT6 sirtuin (silent mating type information regulation 2 homolog) 6 (S. cerevisiae)". 
  3. ^ a b Lombard DB, Schwer B, Alt FW, Mostoslavsky R (February 2008). "SIRT6 in DNA repair, metabolism and ageing". J. Intern. Med. 263 (2): 128–41. doi:10.1111/j.1365-2796.2007.01902.x. PMC 2486832. PMID 18226091. 
  4. ^ Kanfi Y, Naiman S, Amir G, Peshti V, Zinman G, Nahum L, Bar-Joseph Z, Cohen HY (March 2012). "The sirtuin SIRT6 regulates lifespan in male mice". Nature 483 (7388): 218–21. doi:10.1038/nature10815. PMID 22367546. 
  5. ^ Cen Y, Youn DY, Sauve AA (2011). "Advances in characterization of human sirtuin isoforms: chemistries, targets and therapeutic applications". Curr. Med. Chem. 18 (13): 1919–35. doi:10.2174/092986711795590084. PMID 21517779. 
  6. ^ Liu TF, Vachharajani VT, Yoza BK, McCall CE (June 2012). "NAD+-dependent sirtuins 1 and 6 coordinate a switch from glucose to fatty acid oxidation during the acute inflammatory response". J Biol Chem 287 (31): 25758–69. doi:10.1074/jbc.M112.362343. PMID 22700961. 
  7. ^ Van Meter M, Mao Z, Gorbunova V, Seluanov A (September 2011). "SIRT6 overexpression induces massive apoptosis in cancer cells but not in normal cells". Cell Cycle 10 (18): 3153–8. doi:10.4161/cc.10.18.17435. PMC 3218623. PMID 21900744. 

Further reading[edit]

External links[edit]