title: Fates-shifted is an F-box protein that targets Bicoid for degradation and regulates developmental fate determination in Drosophila embryos.
abstract: Bicoid (Bcd) is a morphogenetic protein that instructs patterning along the anterior-posterior (A-P) axis in Drosophila melanogaster embryos. Despite extensive studies, what controls the formation of a normal concentration gradient of Bcd remains an unresolved and controversial question. Here, we show that Bcd protein degradation is mediated by the ubiquitin-proteasome pathway. We have identified an F-box protein, encoded by fates-shifted (fsd), that has an important role in Bcd protein degradation by targeting it for ubiquitylation. Embryos from females lacking fsd have an altered Bcd gradient profile, resulting in a shift of the fatemap along the A-P axis. Our study is an experimental demonstration that, contrary to an alternative hypothesis, Bcd protein degradation is required for normal gradient formation and developmental fate determination.
authors.affiliation: Division of Biomedical Informatics, Cincinnati Children's Research Foundation, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
authors.forename: Junbo
authors.initials: J
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D019521:Body Patterning / Q000235:genetics; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000196:embryology* / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011485:Protein Binding; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; D029721:Drosophila Proteins; D044783:F-Box Proteins; D018398:Homeodomain Proteins; D007976:Leupeptins; D061988:Proteasome Inhibitors; D015534:Trans-Activators; D025801:Ubiquitin; C056478:bcd protein, Drosophila; C556126:fsd protein, Drosophila; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde