The Suppressor of fused gene, involved in Hedgehog signal transduction in Drosophila, is conserved in mammals.
The Suppressor of fused [Su(fu)] gene of Drosophila melanogaster encodes a protein containing a PEST sequence [sequence enriched in proline (P), glutamic acid (E), serine (S) and threonine (T)] which acts as an antagonist to the serine-threonine kinase Fused in Hedgehog (Hh) signal transduction during embryogenesis. The Su(fu) gene isolated from a distantly related Drosophila species, D. virilis, shows significantly high homology throughout its protein sequence with its D. melanogaster counterpart. We show that these two Drosophila homologs of Su(fu) are functionally interchangeable in enhancing the fused phenotype. We have also isolated mammalian homologs of Su(fu). The absence of the PEST sequence in the mammalian Su(fu) protein suggests a different regulation for this product between fly and vertebrates. Using the yeast two-hybrid method, we show that the murine Su(fu) protein can interact directly with the Fused and Cubitus interruptus proteins, known partners of Su(fu) in Drosophila. These data are discussed in the light of their evolutionary relationships.
Institut Jacques Monod, Laboratoire Génétique du Développement et Evolution, Universités Pierre et Marie Curie et Denis Diderot, 2 place Jussieu, F-75251 Paris cedex 05, France.
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Delattre
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Briand
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Paces-Fessy
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Blanchet-Tournier
D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000235:genetics*
D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; D012097:Repressor Proteins; C097059:Su(fu) protein, Drosophila; C490763:Sufu protein, mouse; C077245:hh protein, Drosophila