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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Choi HK,Choi KC,Yoo JY,Song M,Ko SJ,Kim CH,Ahn JH,Chun KH,Yook JI,Yoon HGdoi
10.1016/j.molcel.2011.05.027subject
Has Abstractpub_date
2011-07-22 00:00:00pages
203-16issue
2eissn
1097-2765issn
1097-4164pii
S1097-2765(11)00424-2journal_volume
43pub_type
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