Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition
Authors
Sang Yoon Park ; Hyun Sil Kim ; Nam Hee Kim ; Suena Ji ; So Young Cha ; Jeong Gu Kang ; Ichiro Ota ; Keiji Shimada ; Noboru Konishi ; Hyung Wook Nam ; Soon Won Hong ; Won Ho Yang ; Ju¨ rgen Roth ; Jong In Yook ; Jin Won Cho
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-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. 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.