O-GlcNAc transferase is critical for TLE-mediated repression of canonical Wnt signaling [Glycobiology and Extracellular Matrices]

March 10th, 2014 by Wu, J., Bowe, D. B., Sadlonova, A., Whisenhunt, T. R., Hu, Y., Rustgi, A. K., Nie, Y., Paterson, A. J., Yang, X.

The Drosophila Groucho protein and its mammalian orthologues the transducin-like enhancers of split (TLEs) are critical transcriptional corepressors that repress Wnt and other signaling pathways. Although it is known that Groucho/TLEs are recruited to target genes by pathway-specific transcription factors, molecular events after the corepressor recruitment are largely unclear. We report that association of TLEs with O-GlcNAc transferase, an enzyme that catalyzes posttranslational modification of proteins by O-linked N-acetylglucosamine, is essential for TLE-mediated transcriptional repression. Removal of O-GlcNAc from Wnt-responsive gene promoters is critical for gene activation from Wnt-responsive promoters. Thus, these studies identify a molecular mechanism by which Groucho/TLEs repress gene transcription and provide a model whereby O-GlcNAc may control distinct intracellular signaling pathways.