PMID: 20959806

 

    Legend: Sugar

Title : Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition

Abstract :
  1. Protein O-phosphorylation often occurs reciprocally with O-GlcNAc modification and represents a regulatory principle for proteins
  2. O-phosphorylation of serine by glycogen synthase kinase-3β on Snail1 , a transcriptional repressor of E-cadherin and a key regulator of the epithelial-mesenchymal transition ( EMT ) programme, results in its proteasomal degradation
  3. 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
  4. Hyperglycaemic condition enhances O-GlcNAc modification and initiates EMT by transcriptional suppression of E-cadherin through Snail1
  5. Thus, dynamic reciprocal O-phosphorylation and O-GlcNAc modification of Snail1 constitute a molecular link between cellular glucose metabolism and the control of EMT