Expression and activity of Sirtuins

     Sirtuins are a class of proteins that possess either histone deacetylase or mono-ribosyltransferase activity, and the activities are dependent on and regulated by nicotinamide adenine dinucleotide (NAD+). Until now, seven members have been identified as sirtuin 1 (SIRT1) through SIRT 7. Of which, is considered to be one of the determining factors in longevity induced by calorie restriction.
     SIRT1 is abundantly observed in the brain, such as hypothalamus, cortex, striatum and hippocampus. The level of SIRT1 can be regulated by the transcription factor E2F transcription factor 1(E2F1) under calorie restriction and cellular stresses[1]. Forkhead box proteins (FOXO) are considered to be another group of transcription factors that upregulate SIRT1[2]. Conversely, SIRT1 can deacetylate E2F1 and FOXO, leading to inhibition of E2F1 activity, as well as induction of FOXO activity.
     In addition, SIRT1 expression can be downregulated by hypermethylated in cancer 1 (HIC1) as one of its targets to inhibits SIRT1-mediated p53 inactivation[3]. Recently, PPAR-gama has also been reported to inhibit the expression of SIRT1 by binding to its promoter[4]. Besides, some MicroRNAs or protein can mediate the expression of SIRT at the post-transcriptional level.
     Taken together, the regulators above under certain conditions maintain a certain concentration of SIRT1 by regulating its expression, and thus involve in the regulation of SIRT1 signaling pathway.

[1]. Nat. Cell Biol. 2006; 8, 1025–1031.
[2]. J. Biol. Chem. 2011; 286, 5289–5299.
[3]. Cell 2005; 123, 437–448.
[4]. Nucl. Acids Res. 2010; 38, 7458–7471.