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

Research output: Contribution to journalArticle

103 Citations (Scopus)

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

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Phosphorylation
Epithelial-Mesenchymal Transition
Cadherins
Glycogen Synthase Kinase 3
Degradation
Metabolism
Serine
Proteins
Glucose
Messenger RNA

All Science Journal Classification (ASJC) codes

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

Cite this

Park, S. Y., Kim, H. S., Kim, N. H., Ji, S., Cha, S. Y., Kang, J. G., ... 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
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. / Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition. In: EMBO Journal. 2010 ; Vol. 29, No. 22. pp. 3787-3796.
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Park, SY, Kim, HS, Kim, NH, Ji, S, Cha, SY, Kang, JG, Ota, I, Shimada, K, Konishi, N, Nam, HW, Hong, SW, Yang, WH, Roth, J, Yook, JI & Cho, JW 2010, 'Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition', EMBO Journal, vol. 29, no. 22, pp. 3787-3796. https://doi.org/10.1038/emboj.2010.254

Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition. / 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.

In: EMBO Journal, Vol. 29, No. 22, 17.11.2010, p. 3787-3796.

Research output: Contribution to journalArticle

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AU - Park, Sang Yoon

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AU - Kang, Jeong Gu

AU - Ota, Ichiro

AU - Shimada, Keiji

AU - Konishi, Noboru

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AU - Hong, Soon Won

AU - Yang, Won Ho

AU - Roth, Jürgen

AU - Yook, Jong In

AU - Cho, Jin Won

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AB - 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.

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Park SY, Kim HS, Kim NH, Ji S, Cha SY, Kang JG et al. Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition. EMBO Journal. 2010 Nov 17;29(22):3787-3796. https://doi.org/10.1038/emboj.2010.254