FoxO1 mediates an autofeedback loop regulating SIRT1 expression.

ABSTRACT: Forkhead transcription factor FoxO1 and the NAD(+)-dependent histone deacetylase SIRT1 are evolutionarily conserved regulators of the development of aging, oxidative stress resistance, insulin resistance, and metabolism in species ranging from invertebrates to mammals. SIRT1 deacetylates FoxO1 and enables activation of FoxO1 transcription in multiple systems. The functional consequences of the interactions between FoxO1 and SIRT1 remain incompletely understood. Here, we demonstrate that the 1.5-kb rat sirt1 promoter region contains a cluster of five putative FoxO1 core binding repeat motifs (5×IRS-1) and a forkhead-like consensus binding site (FKHD-L). Luciferase promoter assays demonstrate that FoxO1 directly activates SIRT1 promoter activity and that both the IRS-1 and FKHD-L enable FoxO

SUBMITTER: Xiong S 

PROVIDER: S-EPMC3037641 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature