Hedgehog stimulates maturation of Cubitus interruptus into a labile transcriptional activator.
In Drosophila, signalling by the protein Hedgehog (Hh) alters the activity of the transcription factor Cubitus interruptus (Ci) by inhibiting the proteolysis of full-length Ci (Ci-155) to its shortened Ci-75 form. Ci-75 is found largely in the nucleus and is thought to be a transcriptional repressor, whereas there is evidence to indicate that Ci-155 may be a transcriptional activator. However, Ci-155 is detected only in the cytoplasm, where it is associated with the protein kinase Fused (Fu), with Suppressor of Fused (Su(fu)), and with the microtubule-binding protein Costal-2. It is not clear how Ci-155 might become a nuclear activator. We show here that mutations in Su(fu) cause an increase in the expression of Hh-target genes in a dose-dependent manner while simultaneously reducing Ci-155 concentration by some mechanism other than proteolysis to Ci-75. Conversely, eliminating Fu kinase activity reduces Hh-target gene expression while increasing Ci-155 concentration. We propose that Fu kinase activity is required for Hh to stimulate the maturation of Ci-155 into a short-lived nuclear transcriptional activator and that Su(fu) opposes this maturation step through a stoichiometric interaction with Ci-155.
Ohlmeyer
J T
JT
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Kalderon
D
D
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004330:Drosophila / Q000196:embryology; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D019476:Insect Proteins; D008565:Membrane Proteins; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; C097059:Su(fu) protein, Drosophila; D014157:Transcription Factors; C092937:ci protein, Drosophila; C070844:ptc protein, Drosophila; C110233:slmb protein, Drosophila; C077245:hh protein, Drosophila; D044767:Ubiquitin-Protein Ligases; C085770:fu protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases