Abstract
Members of the Hedgehog (Hh) and Wnt/Wingless (Wg) families of secreted proteins control many aspects of growth and patterning during animal development. Hh signal transduction leads to increased stability of a transcription factor, Cubitus interruptus (Ci), whereas Wg signal transduction causes increased stability of Armadillo (Arm/beta-catenin), a possible co-factor for the transcriptional regulator Lef1/TCF. Here we describe a new gene, slimb (for supernumerary limbs), which negatively regulates both of these signal transduction pathways. Loss of function of slimb results in a cell-autonomous accumulation of high levels of both Ci and Arm, and the ectopic expression of both Hh- and Wg- responsive genes. The slimb gene encodes a conserved F-box/WD40-repeat protein related to Cdc4p, a protein in budding yeast that targets cell-cycle regulators for degradation by the ubiquitin/proteasome pathway. We propose that Slimb protein normally targets Ci and Arm for processing or degradation by the ubiquitin/proteasome pathway, and that Hh and Wg regulate gene expression at least in part by inducing changes in Ci and Arm, which protect them from Slimb-mediated proteolysis.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified
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Armadillo Domain Proteins
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Cell Cycle Proteins / chemistry
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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Cloning, Molecular
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Cyclic AMP-Dependent Protein Kinases / metabolism
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DNA-Binding Proteins / metabolism
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Drosophila / genetics
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Drosophila Proteins*
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F-Box Proteins*
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GTP-Binding Proteins / chemistry
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Gene Expression Regulation, Developmental
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Hedgehog Proteins
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Insect Proteins / chemistry
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Insect Proteins / genetics
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Insect Proteins / metabolism*
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Male
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Molecular Sequence Data
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Mutation
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Proto-Oncogene Proteins / metabolism*
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Signal Transduction*
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Trans-Activators*
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Transcription Factors
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Ubiquitin-Protein Ligases*
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Ubiquitins / metabolism
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Wings, Animal / embryology
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Wnt1 Protein
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beta-Transducin Repeat-Containing Proteins
Substances
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ARM protein, Drosophila
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Armadillo Domain Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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Drosophila Proteins
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F-Box Proteins
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Hedgehog Proteins
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Insect Proteins
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Proto-Oncogene Proteins
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Trans-Activators
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Transcription Factors
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Ubiquitins
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Wnt1 Protein
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beta-Transducin Repeat-Containing Proteins
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ci protein, Drosophila
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slmb protein, Drosophila
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wg protein, Drosophila
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hh protein, Drosophila
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Ubiquitin-Protein Ligases
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Cyclic AMP-Dependent Protein Kinases
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GTP-Binding Proteins