Reversible SUMOylation of TBL1-TBLR1 Regulates β-Catenin-Mediated Wnt Signaling

被引：120

作者：

Choi, Hyo-Kyoung ^{[1
,2
]}

Choi, Kyung-Chul ^{[1
]}

Yoo, Jung-Yoon ^{[1
]}

Song, Meiying ^{[2
,3
]}

Ko, Suk Jin ^{[2
,4
]}

Kim, Chul Hoon ^{[2
,4
]}

Ahn, Jin-Hyun ^{[5
]}

Chun, Kyung-Hee ^{[6
]}

Yook, Jong In ^{[7
]}

Yoon, Ho-Geun ^{[1
,2
]}

机构：

[1] Yonsei Univ, Coll Med, Dept Biochem & Mol Biol, Ctr Chron Metab Dis Res, Seoul 120752, South Korea

[2] Yonsei Univ, Coll Med, Severance Med Res Inst, Brain Korea Project Med Sci 21, Seoul 120752, South Korea

[3] Yonsei Univ, Coll Med, Dept Pathol, Seoul 120752, South Korea

[4] Yonsei Univ, Coll Med, Dept Pharmacol, Seoul 120752, South Korea

[5] Sungkyunkwan Univ, Coll Med, Dept Mol Cell Biol, Suwon 440746, South Korea

[6] Natl Canc Ctr, Res Inst Hosp, Div Translat & Clin Res 2, Genitourinary Canc Branch, Goyang 411769, Gyeonggi, South Korea

[7] Yonsei Univ, Coll Dent, Oral Canc Res Inst, Dept Oral Pathol, Seoul 120752, South Korea

来源：

MOLECULAR CELL | 2011年 / 43卷 / 02期

关键词：

TRANSCRIPTIONAL ACTIVATION; COMPLEX; TBL1; REPRESSION; DESUMOYLATION; STABILIZATION; PROTEINS; PATHWAY; CELLS; HDAC3;

D O I：

10.1016/j.molcel.2011.05.027

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Dysregulation of Wnt signaling has been implicated in tumorigenesis. The role of Transducin beta-like proteins TBL1-TBLR1 in the promotion of Wnt/beta-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-beta-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-beta-catenin complex, leading to inhibition of beta-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.

引用

页码：203 / 216

页数：14

共 35 条

[1]

Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-κB and β-amyloid precursor protein [J].