TY - JOUR
T1 - Xenopus skip modulates Wnt/β-catenin signaling and functions in neural crest induction
AU - Wang, Ying
AU - Fu, Yu
AU - Gao, Lei
AU - Zhu, Guixin
AU - Liang, Juan
AU - Gao, Chan
AU - Huang, Binlu
AU - Fenger, Ursula
AU - Niehrs, Christof
AU - Chen, Ye Guang
AU - Wu, Wei
PY - 2010/4/2
Y1 - 2010/4/2
N2 - The β-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 β-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. Lossof-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 β-catenin signaling, the C-terminally truncated forms of SKIP are able to stabilize β-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 β-catenin transcriptional complex.
AB - The β-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 β-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. Lossof-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 β-catenin signaling, the C-terminally truncated forms of SKIP are able to stabilize β-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 β-catenin transcriptional complex.
UR - http://www.scopus.com/inward/record.url?scp=77951234520&partnerID=8YFLogxK
U2 - 10.1074/jbc.M109.058347
DO - 10.1074/jbc.M109.058347
M3 - Article
C2 - 20103590
AN - SCOPUS:77951234520
SN - 0021-9258
VL - 285
SP - 10890
EP - 10901
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 14
ER -