Figure 1. O-GlcNAcylation Regulates SIRT1 levels in breast cancer cells and mammary epithelial cells in vivo.
(A). Targeting OGT using shRNA results in increased SIRT1 protein levels and activity as measured by increased deacetylation of p53 at lysine-382 in MDA-MB-231 breast cancer cells following immunoblot analysis with indicated antibodies. (B). Treatment with OGT inhibitor Ac-5SGlcNAc (100 μM) for 48 hrs reduces total O-GlcNAc levels and results in elevated SIRT1 protein levels and activity in MDA-MB-231 cells. (C). Treatment with OGA inhibitor NButGT (100 μM) for 48 hours reduces SIRT1 protein levels in breast cancer cells. (D). Stable overexpression of OGT reduces SIRT1 protein levels in MCF7 breast cancer cells. (E). Adenoviral-Cre or control Adenoviral-GFP injections into the mammary fat pad of B6.129-Ogttm1Gwh/J females results in decreased OGT and O- GlcNAc levels and an induction of SIRT1 expression.
