Sirtuin 1
Lua error in Module:Infobox_gene at line 33: attempt to index field 'wikibase' (a nil value). 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 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
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- ↑ 2.0 2.1 Lua error in package.lua at line 80: module 'strict' not found.
- ↑ SIRT1 human gene location in the UCSC Genome Browser.
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Further reading
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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.
