title: The fat tumor suppressor gene in Drosophila encodes a novel member of the cadherin gene superfamily.
abstract: Recessive lethal mutations in the fat locus of Drosophila cause hyperplastic, tumor-like overgrowth of larval imaginal discs, defects in differentiation and morphogenesis, and death during the pupal stage. Clones of mutant cells induced by mitotic recombination demonstrate that the overgrowth phenotype is cell autonomous. Here we show that the fat locus encodes a novel member of the cadherin gene superfamily: an enormous transmembrane protein of over 5000 amino acids with a putative signal sequence, 34 tandem cadherin domains, four EGF-like repeats, a transmembrane domain, and a novel cytoplasmic domain. Two recessive lethal alleles contain alterations in the fat coding sequence, and the dominant fat allele, Gull, contains an insertion of a transposable element in the 33rd cadherin domain. Thus, this novel member of the cadherin gene superfamily functions as a tumor suppressor gene and is required for correct morphogenesis.
authors.affiliation: Howard Hughes Medical Institute, Department of Molecular and Cell Biology, University of California, Berkeley 94720.
authors.forename: P A
authors.initials: PA
authors.lastname: Mahoney
authors.forename: U
authors.initials: U
authors.lastname: Weber
authors.forename: P
authors.initials: P
authors.lastname: Onofrechuk
authors.forename: H
authors.initials: H
authors.lastname: Biessmann
authors.forename: P J
authors.initials: PJ
authors.lastname: Bryant
authors.forename: C S
authors.initials: CS
authors.lastname: Goodman
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics*; D003001:Cloning, Molecular; D004330:Drosophila / Q000196:embryology / Q000235:genetics*; D004475:Ectoderm / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000502:physiology; D005804:Genes, Lethal; D005808:Genes, Recessive; D016147:Genes, Tumor Suppressor; D007814:Larva; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction / Q000379:methods; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014714:Vertebrates
chemical_list: D015820:Cadherins