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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  ;  Ju¨ rgen Roth  ;  Jong In Yook  ;  Jin Won Cho 
 EMBO Journal, Vol.29(22) : 3787-3796, 2010 
Journal Title
 EMBO Journal 
Issue Date
Acetylglucosamine/metabolism* ; Amino Acid Sequence ; Cadherins/genetics ; Cadherins/metabolism ; Cell Line, Tumor ; Cell Movement ; Epithelial-Mesenchymal Transition ; Gene Expression Regulation ; Glucose/metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Hyperglycemia/metabolism* ; Molecular Sequence Data ; Phosphorylation ; Protein Stability ; RNA, Messenger/genetics ; Serine/metabolism ; Snail Family Transcription Factors ; Transcription Factors/genetics ; Transcription Factors/metabolism*
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.
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10.1038/ emboj.2010.254
Appears in Collections:
5. Research Institutes (연구소) > Oral Cancer Research Institute (구강종양연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Kim, Hyun Sil(김현실) ORCID logo https://orcid.org/0000-0003-3614-1764
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Cha, So Young(차소영) ORCID logo https://orcid.org/0000-0002-2810-3883
Hong, Soon Won(홍순원) ORCID logo https://orcid.org/0000-0002-0324-2414
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