Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition.
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.
Park
Sang Yoon
SY
Department of Biology, Yonsei University, Seodaemun-gu, Seoul, Korea.
Kim
Hyun Sil
HS
Kim
Nam Hee
NH
Ji
Suena
S
Cha
So Young
SY
Kang
Jeong Gu
JG
Ota
Ichiro
I
Shimada
Keiji
K
Konishi
Noboru
N
Nam
Hyung Wook
HW
Hong
Soon Won
SW
Yang
Won Ho
WH
Roth
Jürgen
J
Yook
Jong In
JI
Cho
Jin Won
JW
D000117:Acetylglucosamine / Q000378:metabolism*; D000595:Amino Acid Sequence; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D055550:Protein Stability; D012333:RNA, Messenger / Q000235:genetics; D012694:Serine / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D015820:Cadherins; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D012694:Serine; D005947:Glucose; D000117:Acetylglucosamine