Xenopus skip modulates Wnt/beta-catenin signaling and functions in neural crest induction.
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.
Wang
Ying
Y
School of Life Sciences, Protein Science Laboratory of the Ministry of Education, Tsinghua University, Beijing 100084, China.
Fu
Yu
Y
Gao
Lei
L
Zhu
Guixin
G
Liang
Juan
J
Gao
Chan
C
Huang
Binlu
B
Fenger
Ursula
U
Niehrs
Christof
C
Chen
Ye-Guang
YG
Wu
Wei
W
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D007124:Immunoenzyme Techniques; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D009432:Neural Crest / Q000166:cytology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C466999:SPHKAP protein, human; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D051176:beta Catenin; D008156:Luciferases