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

Title
Reversible SUMOylation of TBL1-TBLR1 regulates β-catenin-mediated Wnt signaling.
Authors
Hyo-Kyoung Choi;Kyung-Chul Choi;Ho-Geun Yoon;Jong In Yook;Kyung-Hee Chun;Jin-Hyun Ahn;Chul Hoon Kim;Suk Jin Ko;Meiying Song;Jung-Yoon Yoo
Issue Date
2011
Journal Title
Molecular Cell
ISSN
1097-2765
Citation
Molecular Cell, Vol.43(2) : 203~216, 2011
Abstract
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.
URI
http://www.sciencedirect.com/science/article/pii/S1097276511004242

http://ir.ymlib.yonsei.ac.kr/handle/22282913/93487
DOI
10.1016/j.molcel.2011.05.027
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Biochemistry & Molecular Biology
1. 연구논문 > 2. College of Dentistry > Dept. of Oral Pathology
1. 연구논문 > 1. College of Medicine > Dept. of Pharmacology
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
Yonsei Authors
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