Sirtuin 1

Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a is_associated_with::protein that in humans is encoded by the SIRT1 is_associated_with::gene.

SIRT1 stands for sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae), referring to the fact that its is_associated_with::sirtuin homolog (biological equivalent across species) in yeast (S. cerevisiae) is Sir2. SIRT1 is an is_associated_with::enzyme that deacetylates proteins that contribute to cellular regulation (reaction to stressors, longevity).

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.

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

Activators

 * is_associated_with::Lamin A is a protein that had been identified as a direct activator of Sirtuin 1 during a study on is_associated_with::Progeria.
 * is_associated_with::Resveratrol has been claimed to be an activator of Sirtuin 1, 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. Resveratrol increases the expression of SIRT1, meaning that it does increase the activity of SIRT1, though not necessarily by direct activation. However, resveratrol was later shown to directly activate Sirtuin 1 against non-modified peptide substrates.  Resveratrol also enhances the binding between Sirtuin 1 and is_associated_with::Lamin A.
 * is_associated_with::SRT-1720 was also claimed to be an activator, but this now has been questioned.

Interactions
Sirtuin 1 has been shown to interact with is_associated_with::HEY2, PGC1-alpha, and is_associated_with::ERR-alpha. is_associated_with::Mir-132 microRNA has been reported to interact with Sirtuin 1 mRNA, so as to reduce protein expression. This has been linked to is_associated_with::insulin resistance in the obese.

Human Sirt1 has been reported having 136 direct interactions in Interactomic studies involved in numerous processes.