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

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82 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)203-216
Number of pages14
JournalMolecular Cell
Volume43
Issue number2
DOIs
Publication statusPublished - 2011 Jul 22

Bibliographical note

Funding Information:
This work was supported by a National Foundation grant funded by the Korea government (MEST) (numbers 2010-0028367 and 2010-0002430). The authors thank D.S. Jang for his excellent support with medical illustration.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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