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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / antagonists & inhibitors
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Blotting, Western
  • Chromatin Immunoprecipitation
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Regulation, Developmental*
  • Gene Library
  • HeLa Cells
  • Humans
  • Immunoenzyme Techniques
  • Luciferases / metabolism
  • Mice
  • Neural Crest / cytology
  • Neural Crest / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism*
  • Xenopus laevis
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • Adaptor Proteins, Signal Transducing
  • RNA, Messenger
  • RNA, Small Interfering
  • SPHKAP protein, human
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • beta Catenin
  • Luciferases