title: Suppressor of Fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex.
abstract: The Suppressor of Fused [Su(fu)] protein plays a conserved role in the regulation of Gli transcription factors of the hedgehog (Hh) signaling pathway that controls cell fate and tissue patterning during development. In both Drosophila and mammals, Su(fu) represses Gli-mediated transcription, but the mode of its action is not completely understood. Recent evidence suggests that Su(fu) physically interacts with the Gli proteins and, when overexpressed, sequesters Gli in the cytoplasm. However, Su(fu) also traverses into the nucleus under the influence of a serine-threonine kinase, Fused (Fu), and has the ability to form a DNA-binding complex with Gli, suggesting that it has a nuclear function. Here we report that the mouse homolog of Su(fu) [mSu(fu)] specifically interacts with SAP18, a component of the mSin3 and histone deacetylase complex. In addition, we demonstrate that mSu(fu) functionally cooperates with SAP18 to repress transcription by recruiting the SAP18-mSin3 complex to promoters containing the Gli-binding element. These results provide biochemical evidence that Su(fu) directly participates in modulating the transcriptional activity of Gli.
authors.affiliation: G. W. Hooper Foundation and Department of Microbiology and Immunology, University of California, San Francisco, CA 94143-0552, USA. stevenyancheng@yahoo.com
authors.forename: Steven Yan
authors.initials: SY
authors.lastname: Cheng
authors.forename: J Michael
authors.initials: JM
authors.lastname: Bishop
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002352:Carrier Proteins; D002467:Cell Nucleus / Q000378:metabolism; D056970:Co-Repressor Proteins; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004330:Drosophila; D029721:Drosophila Proteins; D015723:Gene Library; D005982:Glutathione Transferase / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D015513:Oncogene Proteins / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D016601:RNA-Binding Proteins; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques; D000071676:Zinc Finger Protein GLI1
chemical_list: D002352:Carrier Proteins; D056970:Co-Repressor Proteins; D018076:DNA, Complementary; D029721:Drosophila Proteins; D015513:Oncogene Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; C498650:SAP18 protein, human; C071731:SIN3 protein, S cerevisiae; C490764:SUFU protein, human; D029701:Saccharomyces cerevisiae Proteins; C097059:Su(fu) protein, Drosophila; C490763:Sufu protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; C407043:bicoid interacting protein 1, Drosophila; D005982:Glutathione Transferase; D006655:Histone Deacetylases