The Drosophila F-box protein Archipelago controls levels of the Trachealess transcription factor in the embryonic tracheal system.
The archipelago gene (ago) encodes the F-box specificity subunit of an SCF(skp-cullin-f box) ubiquitin ligase that inhibits cell proliferation in Drosophila melanogaster and suppresses tumorigenesis in mammals. ago limits mitotic activity by targeting cell cycle and cell growth proteins for ubiquitin-dependent degradation, but the diverse developmental roles of other F-box proteins suggests that it is likely to have additional protein targets. Here we show that ago is required for the post-mitotic shaping of the Drosophila embryonic tracheal system, and that it acts in this tissue by targeting the Trachealess (Trh) protein, a conserved bHLH-PAS transcription factor. ago restricts Trh levels in vivo and antagonizes transcription of the breathless FGF receptor, a known target of Trh in the tracheal system. At a molecular level, the Ago protein binds Trh and is required for proteasome-dependent elimination of Trh in response to expression of the Dysfusion protein. ago mutations that elevate Trh levels in vivo are defective in binding forms of Trh found in Dysfusion-positive cells. These data identify a novel function for the ago ubiquitin-ligase in tracheal morphogenesis via Trh and its target breathless, and suggest that ago has distinct functions in mitotic and post-mitotic cells that influence its role in development and disease.
Mortimer
Nathan T
NT
Department of Cell Biology, Emory University School of Medicine, 615 Michael St. WBRB 442, Atlanta, GA 30322, USA.
Moberg
Kenneth H
KH
D000818:Animals; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D008856:Microscopy, Fluorescence; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D014132:Trachea / Q000196:embryology*; D014157:Transcription Factors / Q000378:metabolism*
D029721:Drosophila Proteins; D044783:F-Box Proteins; D017468:Receptors, Fibroblast Growth Factor; D014157:Transcription Factors; C488876:ago protein, Drosophila; C099995:trh protein, Drosophila; C102301:BTL protein, Drosophila; D011505:Protein-Tyrosine Kinases