SIRT6

SIRT6

A gene on chromosome 19p13.3 that encodes an NAD-dependent protein deacetylase that acts on Lys-9 of histone H3 at NF-kappaB target promoters, downregulating a subset of NF-kappaB target genes. Its deacetylation of nucleosomes interferes with RELA binding to target DNA. It may be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance and genomic stability. It is required for normal IGF1 serum levels and glucose homeostasis. SIRT 6 modulates cell senescence and apoptosis and regulates TNF production.
References in periodicals archive ?
SIRT6 promotes DNA repair under stress by activating PARP1.
The histone deacetylase SIRT6 controls embryonic stem cell fate via TET-mediated production of 5-hydroxymethylcytosine.
In contrast, SIRT6 protein levels are reported to be moderately increased in the same arthritis experimental model (12).
BGU researchers have determined in mouse models that high levels of SIRT6 contribute to DNA repair while low levels permit DNA damage accumulation.
Transgenic mice overexpressing SIRT6 exhibit a significantly longer life span, while the SIRT6-deficient mice have severe metabolic defects, developed ageing-like phenotypes by 2-3 weeks of age, and eventually died at about 4 weeks [5, 8].
SIRT4 and SIRT6 function as mono-ADP-ribosyltransferases, which transfer the ADP-ribosyl moiety to the substrate protein including glutamate dehydrogenase 1, poly (ADP-ribose) polymerase 1 respectively.
In addition, while the expression levels of histone deacetylases such as HDAC1, SIRT1 and SIRT6 are increased in IMR 90 cells in the presence of scopoletin, the expression levels of histone acetyltransferases are decreased.
Recently, it was reported that overexpression of Sir2 homologue SIRT6 extended the lifespan of male mice.
According to the new joint study by the University of Michigan Health System and Harvard Medical School, loss of the SIRT6 protein in mice increases the number, size and aggressiveness of tumors.
By increasing SIRT6 levels, cells were able to stimulate their ability to repair double strand breaks.
One involved a molecule known as SIRT6 -- a member of the sirtuin family of proteins that modulate life span in organisms such as yeast and worms -- that Chua's laboratory has been studying for several years.
Mostoslavsky, however, is most interested in the effect of SIRT6 on cancer.