title: O-GlcNAc transferase is critical for transducin-like enhancer of split (TLE)-mediated repression of canonical Wnt signaling.
abstract: 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.
authors.affiliation: Center for Mitochondrial Biology and Medicine, the Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China; Section of Comparative Medicine and Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06519.
authors.forename: Jing
authors.initials: J
authors.lastname: Wu
authors.affiliation: Division of Endocrinology and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Damon B
authors.initials: DB
authors.lastname: Bowe
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322.
authors.forename: Andrea
authors.initials: A
authors.lastname: Sadlonova
authors.affiliation: Division of Endocrinology and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Whisenhunt
authors.affiliation: Division of Endocrinology and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Medicine (GI) and Genetics, Abramson Cancer Center, 600 CRB, University of Pennsylvania, Philadelphia, Pennsylvania 19104.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Rustgi
authors.affiliation: State Key Laboratory of Cancer Biology and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 127 West Changle Road, Xi'an, Shaanxi 710032, China.
authors.forename: Yongzhan
authors.initials: Y
authors.lastname: Nie
authors.affiliation: Division of Endocrinology and Metabolism, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Paterson
authors.affiliation: Section of Comparative Medicine and Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06519. Electronic address: xiaoyong.yang@yale.edu.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers; D004330:Drosophila; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D015293:Transducin / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D017931:DNA Primers; D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D015293:Transducin
keywords: Gene Silencing; Groucho/TLE; O-GlcNAc; OGT; Signal Transduction; Transcription Repressor; Wnt Pathway