title: Drosophila TGIF proteins are transcriptional activators.
abstract: The information carried by transforming growth factor beta (TGF-beta) signaling molecules induces profound responses in target cells. To restrict this information to appropriate cells, TGF-beta signaling pathways are tightly regulated by dynamic interactions with transcriptional activators and repressors. Numerous cross-species experiments have shown that TGF-beta family members and their signal transduction machinery (receptors and Smad signal transducers) are functionally conserved between vertebrates and invertebrates. TG-interacting factor (TGIF) is a homeodomain-containing transcriptional corepressor of TGF-beta-dependent gene expression in mammals that is associated with holoprosencephaly in humans. Here we report a biochemical analysis of TGIF from zebra fish and Drosophila. Our study reveals an unprecedented role reversal between vertebrate and invertebrate TGIF proteins. Zebra fish TGIF, like its mammalian relative, interacts with general corepressors and represses TGF-beta-responsive gene expression. We identified a tandem duplication of TGIF genes in Drosophila. In contrast to vertebrate TGIFs, both Drosophila TGIFs strongly activate transcription. We also demonstrate that Drosophila TGIF proteins physically interact with both Mad and dSmad2, suggesting a role in Dpp and activin signaling. Thus, dTGIF may be the first transcription factor in the Drosophila activin pathway. Overall, our study suggests that assumptions about the functional equivalence of conserved proteins must be validated experimentally.
authors.affiliation: Department of Biochemistry and Molecular Genetics, and Center for Cell Signaling, University of Virginia, Charlottesville, VA 22908, USA.
authors.forename: Cathy A
authors.initials: CA
authors.lastname: Hyman
authors.forename: Laurent
authors.initials: L
authors.lastname: Bartholin
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Newfeld
authors.forename: David
authors.initials: D
authors.lastname: Wotton
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism; D004330:Drosophila / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D018398:Homeodomain Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051899:Smad2 Protein; D013045:Species Specificity; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014714:Vertebrates
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; C112506:MAD protein, Drosophila; D051899:Smad2 Protein; D015534:Trans-Activators; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C476930:achi protein, Drosophila