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Snail1 is Stabilized by O-GlcNAc Modification in Hyperglycemic Condition and Causes Epithelial-Mesenchymal Transition

초록

영어

Protein O-phosphorylation can occur reciprocal with O-GlcNAc modification and represents a regulatory principle for proteins. O-phosphorylation of serine by GSK-3β on Snail1, a transcriptional repressor of E-cadherin and a key regulator of the epithelial-mesenchymal transition (EMT) program, results in its proteasomal degradation. We show that Snail1 carries O-GlcNAc at serine112 that stabilizes it by suppressing O-phosphorylation-mediated degradation. Stabilization by O-GlcNAc of Snail1 results in attenuation of E-cadherin mRNA expression. Enhanced O-GlcNAc modification occurred under hyperglycemic conditions and initiated EMT by transcriptional suppression of E-cadherin through Snail1. Thus, a molecular link exists between cellular glucose metabolism and the control of EMT by dynamic reciprocal O-phosphorylation and O-GlcNAc modification of Snail1.

저자정보

  • Sang Yoon Park Department of Biology and These authors contributed equally to this work
  • Hyun Sil Kim Department of Oral Pathology, Oral Cancer Research Institute, College of Dentistry Yonsei University, These authors contributed equally to this work
  • Nam Hee Kim Department of Oral Pathology, Oral Cancer Research Institute, College of Dentistry Yonsei University
  • Suena Ji Department of Biology
  • So Young Cha Department of Oral Pathology, Oral Cancer Research Institute, College of Dentistry Yonsei University
  • Jeong Gu Kang Department of Biology
  • Ichiro Ota Departments of Otolaryngology
  • Keiji Shimada Pathology, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8522 Japan,
  • Noboru Konishi Pathology, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8522 Japan
  • Hyung Wook Nam Department of Biochemistry, Yonsei University
  • Won Ho Yang Department of Biology
  • Jürgen Roth WCU Program of Graduate School, Department of Biomedical Science, Yonsei University
  • Jong In Yook Department of Oral Pathology, Oral Cancer Research Institute, College of Dentistry Yonsei University
  • Jin Won Cho Department of Biology and WCU Program of Graduate School, Department of Biomedical Science, Yonsei University

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