
Identification of a cellularly active SIRT6 allosteric activator - Nature
2018年10月29日 · SIRT6, a member of the SIRT deacetylase family, is responsible for deacetylation of histone H3 Nε -acetyl-lysines 9 (H3K9ac) and 56 (H3K56ac). As a tumor suppressor, SIRT6 has frequently been...
Discovery of a potent and highly selective inhibitor of SIRT6 …
2024年3月1日 · Here, we developed a novel SIRT6 allosteric inhibitor, compound 11e, with maximal inhibitory potency and an IC 50 value of 0.98 ± 0.13 μmol/L. Moreover, compound 11e exhibited significant selectivity against other histone deacetylases (HADC1‒11 and SIRT1‒3) at concentrations up to 100 μmol/L.
Targeting a cryptic allosteric site of SIRT6 with small-molecule ...
2022年2月1日 · SIRT6 belongs to the conserved NAD +-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases.
Cytoplasmic SIRT6-mediated ACSL5 deacetylation impedes
2022年11月3日 · Histone deacetylase Sirtuin 6 (SIRT6) regulates NAFLD by regulating metabolism-related gene expression, but an extrachromosomal role for SIRT6 in NAFLD development remains elusive. We investigated whether SIRT6 functions on NAFLD in the cytoplasm. We found that SIRT6 binds saturated fatty acids, especially palmitic acid.
Structural basis for the activation and inhibition of Sirtuin 6 by ...
2019年12月16日 · Mammalian Sirtuin 6 (Sirt6) is an NAD + -dependent protein deacylase regulating metabolism and chromatin homeostasis. Sirt6 activation protects against metabolic and aging-related diseases,...
Discovery of 5-(4-methylpiperazin-1-yl)-2-nitroaniline derivatives …
2020年8月15日 · SIRT6 is a deacetylase of histone H3 and inhibitors of SIRT6 have been thought as potential agents for treatment of diabetes. Herein we report the discovery of a series of new SIRT6 inhibitors containing the skeleton 1-phenylpiperazine.
Natural polyphenols as sirtuin 6 modulators | Scientific Reports
2018年3月7日 · Because SIRT6 has been implicated in longevity, metabolism, DNA-repair, and inflammatory response reduction, it is an interesting target in inflammatory and metabolic diseases as well as in...
SIRT6 transcriptionally regulates global protein synthesis …
Here, we report that SIRT6, a nuclear-localized histone deacetylase represses global protein synthesis by transcriptionally regulating mTOR signalling via the transcription factor Sp1, independent of its deacetylase activity. Our results suggest that SIRT6 deficiency increases protein synthesis in mice.
Reciprocal Regulation between SIRT6 and miR-122 Controls Liver ...
2016年1月12日 · To experimentally measure affinity of miR-122 and SIRT6 association, surface plasmon resonance (SPR) assay was used to examine the binding parameters of miR-122 with several putative binding sites on SIRT6 3′ UTR (miR-122-BS1 to BS3) and the full length SIRT6 3′ UTR (510 bp) (Figures 2A–2D).
SIRT6 is a DNA double-strand break sensor - PMC - PubMed …
SIRT6 relocates to sites of damage independently of signaling and known sensors. It activates downstream signaling for DSB repair by triggering ATM recruitment, H2AX phosphorylation and the recruitment of proteins of the homologous recombination and …