earticle

영어

X -linked inhibitor of apoptosis (XIAP), an inhibitor of apoptotic cell death, has a RING domain and functions as an E3 ligase, catalysing the ubiquitination of various substrates such as apoptosis-inducing factor, TGF- [3-activated kinase 1, and MEK kinase 2. Here, we identified 0-linked N-acetylglucosamine ( 0-GlcNAc) transferase ( OGT) as a substrate of XIAP. We showed that OGT catalyses the 0-GlcNAc modification of XIAP at serine 406, and this modification regulates the E3 ligase activity of XIAP towards OGT. Substitution of XIAP Ser406 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 XIAP requires 0-GlcNAcylation in the regulation of its E3 ligase activity toward OGT, which leads to OGT degradation and the inhibition of cancer cell growth.