원문정보
초록
영어
Protein O-phosphorylation can occur reciprocal with O-GlcNAc modification and represents a regulatory principle for proteins. O-phosphorylation of serine by GSK-3β on Snail1, a transcriptional repressor of E-cadherin and a key regulator of the epithelial-mesenchymal transition (EMT) program, results in its proteasomal degradation. We show that Snail1 carries O-GlcNAc at serine112 that stabilizes it by suppressing O-phosphorylation-mediated degradation. Stabilization by O-GlcNAc of Snail1 results in attenuation of E-cadherin mRNA expression. Enhanced O-GlcNAc modification occurred under hyperglycemic conditions and initiated EMT by transcriptional suppression of E-cadherin through Snail1. Thus, a molecular link exists between cellular glucose metabolism and the control of EMT by dynamic reciprocal O-phosphorylation and O-GlcNAc modification of Snail1.