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


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.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC2856295 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature

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

Wang Ying Y   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  

The Journal of biological chemistry 20100126 14


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  ...[more]

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