J Biol Chem. 2010 Apr 2;285(14):10890-901. doi: 10.1074/jbc.M109.058347. Epub 2010 Jan 26.

Xenopus skip modulates Wnt/beta-catenin signaling and functions in neural crest induction.

Wang Y1, Fu Y, Gao L, Zhu G, Liang J, Gao C, Huang B, Fenger U, Niehrs C, Chen YG, Wu W.

Author information

1School of Life Sciences, Protein Science Laboratory of the Ministry of Education, Tsinghua University, Beijing 100084, China.

Abstract

The beta-catenin-lymphoid enhancer factor (LEF) protein complex is the key mediator of canonical Wnt signaling and initiates target gene transcription upon ligand stimulation. In addition to beta-catenin and LEF themselves, many other proteins have been identified as necessary cofactors. Here we report that the evolutionally conserved splicing factor and transcriptional co-regulator, SKIP/SNW/NcoA62, forms a ternary complex with LEF1 and HDAC1 and mediates the repression of target genes. Loss-of-function studies showed that SKIP is obligatory for Wnt signaling-induced target gene transactivation, suggesting an important role of SKIP in the canonical Wnt signaling. Consistent with its involvement in beta-catenin signaling, the C-terminally truncated forms of SKIP are able to stabilize beta-catenin and enhance Wnt signaling. In Xenopus embryos, both overexpression and knockdown of Skip lead to reduced neural crest induction, consistent with down-regulated Wnt signaling in both cases. Our results indicate that SKIP is a novel component of the beta-catenin transcriptional complex.

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