Premium
Snail1 is stabilized by O ‐GlcNAc modification in hyperglycaemic condition
Author(s) -
Park Sang Yoon,
Kim Hyun Sil,
Kim Nam Hee,
Ji Suena,
Cha So Young,
Kang Jeong Gu,
Ota Ichiro,
Shimada Keiji,
Konishi Noboru,
Nam Hyung Wook,
Hong Soon Won,
Yang Won Ho,
Roth Jürgen,
Yook Jong In,
Cho Jin Won
Publication year - 2010
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2010.254
Subject(s) - biology , computational biology , biochemistry
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.