The ubiquitin ligase Hyperplastic discs negatively regulates hedgehog and decapentaplegic expression by independent mechanisms.
Photoreceptor differentiation in the Drosophila eye disc progresses from posterior to anterior in a wave driven by the Hedgehog and Decapentaplegic signals. Cells mutant for the hyperplastic discs gene misexpress both of these signaling molecules in anterior regions of the disc, leading to premature photoreceptor differentiation and overgrowth of surrounding tissue. The two genes are independently regulated by hyperplastic discs; decapentaplegic can still be misexpressed in cells mutant for both hyperplastic discs and hedgehog, and a repressor form of the transcription factor Cubitus interruptus can block decapentaplegic misexpression but not hedgehog misexpression. Loss of hyperplastic discs causes the accumulation of full-length Cubitus interruptus protein, but not of Smoothened, in both the eye and wing discs. hyperplastic discs encodes a HECT domain E3 ubiquitin ligase that is likely to act by targeting Cubitus interruptus and an unknown activator of hedgehog expression for proteolysis.
Lee
Jeffrey D
JD
Skirball Institute of Biomolecular Medicine and Department of Cell Biology, NYU School of Medicine, 540 First Avenue, New York, NY 10016, USA.
Amanai
Kazuhito
K
Shearn
Allen
A
Treisman
Jessica E
JE
D000818:Animals; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000502:physiology*; D004331:Drosophila melanogaster; D053823:Hedgehog Proteins; D007150:Immunohistochemistry; D008025:Ligases / Q000096:biosynthesis* / Q000378:metabolism* / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009154:Mutation; D010453:Peptide Synthases / Q000096:biosynthesis* / Q000502:physiology*; D010641:Phenotype; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D053823:Hedgehog Proteins; D014157:Transcription Factors; D025801:Ubiquitin; C092937:ci protein, Drosophila; C064196:dpp protein, Drosophila; C077245:hh protein, Drosophila; C117617:UBR5 protein, human; C471151:hyd protein, Drosophila; D044767:Ubiquitin-Protein Ligases; D008025:Ligases; D010453:Peptide Synthases