Vitamin D induces SIRT1 activation through K610 deacetylation in colon cancer.

ABSTRACT: Posttranslational modifications of epigenetic modifiers provide a flexible and timely mechanism for rapid adaptations to the dynamic environment of cancer cells. SIRT1 is an NAD⁺-dependent epigenetic modifier whose activity is classically associated with healthy aging and longevity, but its function in cancer is not well understood. Here, we reveal that 1α,25-dihydroxyvitamin D₃ (1,25(OH)₂D_3, calcitriol), the active metabolite of vitamin D (VD), promotes SIRT1 activation through auto-deacetylation in human colon carcinoma cells, and identify lysine 610 as an essential driver of SIRT1 activity. Remarkably, our data show that the post-translational control of SIRT1 activity mediates the antiproliferative action of 1,25(OH)₂D₃.

SUBMITTER: Garcia-Martinez JM 

PROVIDER: S-EPMC10396337 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature