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Reversible SUMOylation of TBL1-TBLR1 regulates β-catenin-mediated Wnt signaling.

 Hyo-Kyoung Choi  ;  Kyung-Chul Choi  ;  Jung-Yoon Yoo  ;  Meiying Song  ;  Suk Jin Ko  ;  Chul Hoon Kim  ;  Jin-Hyun Ahn  ;  Kyung-Hee Chun  ;  Jong In Yook  ;  Ho-Geun Yoon 
 MOLECULAR CELL, Vol.43(2) : 203-216, 2011 
Journal Title
Issue Date
3T3 Cells ; Animals ; Humans ; Mice ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism* ; Receptors, Cytoplasmic and Nuclear/metabolism ; Repressor Proteins/metabolism ; Signal Transduction* ; Sumoylation ; Transducin/genetics ; Transducin/metabolism ; Transfection ; Tumor Cells, Cultured ; Wnt Proteins/genetics ; Wnt Proteins/metabolism* ; beta Catenin/genetics ; beta Catenin/metabolism*
Dysregulation of Wnt signaling has been implicated in tumorigenesis. The role of Transducin β-like proteins TBL1-TBLR1 in the promotion of Wnt/β-catenin-mediated oncogenesis has recently been emphasized; however, the molecular basis of activation of Wnt signaling by the corepressor TBL1-TBLR1 is incompletely understood. Here, we show that both TBL1 and TBLR1 are SUMOylated in a Wnt signaling-dependent manner, and that this modification is selectively reversed by SUMO-specific protease I (SENP1). SUMOylation dismissed TBL1-TBLR1 from the nuclear hormone receptor corepressor (NCoR) complex, increased recruitment of the TBL1-TBLR1-β-catenin complex to the promoter of Wnt target genes, and consequently led to activation of Wnt signaling. Conversely, SENP1 decreased formation of the TBL1-TBLR1-β-catenin complex, leading to inhibition of β-catenin-mediated transcription. Importantly, inhibition of SUMOylation significantly decreased the tumorigenicity of SW480 colon cancer cells. Thus, our data reveal a mechanism for activation of Wnt signaling via the SUMOylation-dependent disassembly of the corepressor complex.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Kim, Chul Hoon(김철훈) ORCID logo https://orcid.org/0000-0002-7360-429X
Yoo, Jung Yoon(유정윤) ORCID logo https://orcid.org/0000-0001-9366-3863
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
Yoon, Ho Geun(윤호근) ORCID logo https://orcid.org/0000-0003-2718-3372
Choi, Kyung Chul(최경철)
Choi, Hyo Kyoung(최효경)
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