Protein O-phosphorylation often occurs reciprocally with O-GlcNAc modification and represents a regulatory principle for proteins. O-phosphorylation of serine by glycogen synthase kinase-3Î 2 on Snail1, a transcriptional repressor of E-cadherin and a key regulator of the epithelialĝ€"mesenchymal transition (EMT) programme, results in its proteasomal degradation. We show that by suppressing O-phosphorylation- mediated degradation, O-GlcNAc at serine112 stabilizes Snail1 and thus increases its repressor function, which in turn attenuates E-cadherin mRNA expression. Hyperglycaemic condition enhances O-GlcNAc modification and initiates EMT by transcriptional suppression of E-cadherin through Snail1. Thus, dynamic reciprocal O-phosphorylation and O-GlcNAc modification of Snail1 constitute a molecular link between cellular glucose metabolism and the control of EMT.
|Number of pages||10|
|Publication status||Published - 2010 Nov 17|
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Biochemistry, Genetics and Molecular Biology(all)
- Immunology and Microbiology(all)