원문정보
초록
영어
XIAP (X-linked inhibitor of apoptosis) is an inhibitor of apoptotic cell death. It consists of a RING domain and functions as an E3 ligase. In this study, we identify OGT (O-linked N-acetylglucosamine (O-GlcNAc) Transferase) as a substrate of XIAP. In addition, we show that OGT catalyses the O-GlcNAcylation XIAP at serine 406, and that this modification in turn regulates the E3 ligase activity of XIAP towards OGT. Substitution of XIAP serine 406 by alanine decreased its E3 ligase activity toward OGT but not toward other substrates. Stable overexpression of XIAP in HCT116 human colorectal carcinoma cells decreased OGT protein levels and inhibited cancer cell growth and invasion. These results suggest that O-GlcNAcylation of XIAP is required for its E3 ligase activity toward OGT, which leads to OGT degradation and ultimately the inhibition of cancer cell growth.