title: Vertebrate homologs of Drosophila suppressor of fused interact with the gli family of transcriptional regulators.
abstract: The hedgehog (Hh) signaling pathway is crucial for pattern formation during metazoan development. Although originially characterized in Drosophila, vertebrate homologs have been identified for several, but not all, genes in the pathway. Analysis of mutants in Drosophila demonstrates that Suppressor of fused [Su(fu)] interacts genetically with genes encoding proteins in the Hh signal transduction pathway, and its protein product physically interacts with two of the proteins in the Hh pathway. We report here the molecular cloning and characterization of chicken and mouse homologs of Su(fu). The chick and mouse proteins are 27% identical and 53% similar at the amino acid level to the Drosophila melanogaster and Drosophila virilis proteins. Vertebrate Su(fu) is widely expressed in the developing embryo with higher levels in tissues that are known to be patterned by Hh signaling. The chick Su(fu) protein can physically interact with factors known to function in Hh signal transduction including the Drosophila serine/threonine kinase, Fused, and the vertebrate transcriptional regulators Gli1 and Gli3. This interaction may be significant for transcriptional regulation, as recombinant Su(fu) enhances the ability of Gli proteins to bind DNA in electrophoretic mobility shift assays.
authors.affiliation: Department of Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts, 02115, USA.
authors.forename: R V
authors.initials: RV
authors.lastname: Pearse
authors.forename: L S
authors.initials: LS
authors.lastname: Collier
authors.forename: M P
authors.initials: MP
authors.lastname: Scott
authors.forename: C J
authors.initials: CJ
authors.lastname: Tabin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D015870:Gene Expression; D053823:Hedgehog Proteins; D019476:Insect Proteins / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D029867:Xenopus Proteins; D000071676:Zinc Finger Protein GLI1; D000074290:Zinc Finger Protein Gli3
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D019476:Insect Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D015513:Oncogene Proteins; D010446:Peptide Fragments; D011506:Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; C490764:SUFU protein, human; C490763:Sufu protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D000071676:Zinc Finger Protein GLI1; D000074290:Zinc Finger Protein Gli3; C077245:hh protein, Drosophila