SIRT1 is a transcriptional enhancer of the glucocorticoid receptor acting independently to its deacetylase activity.

ABSTRACT: Glucocorticoids have strong effects on diverse human activities through the glucocorticoid receptor (GR). Sirtuin 1 (SIRT1) is a NAD⁺-dependent histone deacetylase and promotes longevity by influencing intermediary metabolism and other regulatory activities including mitochondrial function. In this study, we examined the effects of SIRT1 on GR-mediated transcriptional activity. We found that SIRT1 enhanced GR-induced transcriptional activity on endogenous and exogenous glucocorticoid-responsive genes, whereas knockdown of SIRT1 attenuated it. This effect of SIRT1 was independent to its deacetylase activity, as the SIRT1 mutant defective in this activity (H363Y) enhanced GR transcriptional activity, and the compounds inhibiting or activating the SIRT1 deacetylase activity did not

SUBMITTER: Suzuki S 

PROVIDER: S-EPMC5756502 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature