Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition

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, Jürgen Roth, Jong In Yook, Jin Won Cho

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Abstract

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.

Original languageEnglish
Pages (from-to)3787-3796
Number of pages10
JournalEMBO Journal
Volume29
Issue number22
DOIs
Publication statusPublished - 2010 Nov 17

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Park, S. Y., Kim, H. S., Kim, N. H., Ji, S., Cha, S. Y., Kang, J. G., Ota, I., Shimada, K., Konishi, N., Nam, H. W., Hong, S. W., Yang, W. H., Roth, J., Yook, J. I., & Cho, J. W. (2010). Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition. EMBO Journal, 29(22), 3787-3796. https://doi.org/10.1038/emboj.2010.254