Expression of the vertebrate Gli proteins in Drosophila reveals a distribution of activator and repressor activities.
The Cubitus interruptus (Ci) and Gli proteins are transcription factors that mediate responses to Hedgehog proteins (Hh) in flies and vertebrates, respectively. During development of the Drosophila wing, Ci transduces the Hh signal and regulates transcription of different target genes at different locations. In vertebrates, the three Gli proteins are expressed in overlapping domains and are partially redundant. To assess how the vertebrate Glis correlate with Drosophila Ci, we expressed each in Drosophila and monitored their behaviors and activities. We found that each Gli has distinct activities that are equivalent to portions of the regulatory arsenal of Ci. Gli2 and Gli1 have activator functions that depend on Hh. Gli2 and Gli3 are proteolyzed to produce a repressor form able to inhibit hh expression. However, while Gli3 repressor activity is regulated by Hh, Gli2 repressor activity is not. These observations suggest that the separate activator and repressor functions of Ci are unevenly partitioned among the three Glis, yielding proteins with related yet distinct properties.
Aza-Blanc
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P
Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.
Lin
H Y
HY
Ruiz i Altaba
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A
Kornberg
T B
TB
D000818:Animals; D030801:Animals, Genetically Modified; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D006801:Humans; D019476:Insect Proteins / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011898:Ranidae; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014921:Wings, Animal / Q000033:anatomy & histology; D029867:Xenopus Proteins; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C082593:GLI2 protein, human; C108003:GLI3 protein, Xenopus; C065683:GLI3 protein, human; C000618551:Gli2 protein, mouse; C465571:Gli3 protein, mouse; D053823:Hedgehog Proteins; D019476:Insect Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D011506:Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D029867:Xenopus Proteins; D000071676:Zinc Finger Protein GLI1; D000075746:Zinc Finger Protein Gli2; D000074290:Zinc Finger Protein Gli3; C092937:ci protein, Drosophila; C077245:hh protein, Drosophila; C085770:fu protein, Drosophila; D017346:Protein Serine-Threonine Kinases