Ecdysone-induced expression of the caspase DRONC during hormone-dependent programmed cell death in Drosophila is regulated by Broad-Complex.
The steroid hormone ecdysone regulates both cell differentiation and cell death during insect metamorphosis, by hierarchical transcriptional regulation of a number of genes, including the Broad-Complex (BR-C), the zinc finger family of transcription factors. These genes in turn regulate the transcription of a number of downstream genes. DRONC, a key apical caspase in Drosophila, is the only known caspase that is transcriptionally regulated by ecdysone during development. We demonstrate that dronc gene expression is ablated or reduced in BR-C mutant flies. Using RNA interference in an ecdysone-responsive Drosophila cell line, we show that DRONC is essential for ecdysone-mediated cell death, and that dronc upregulation in these cells is controlled by BR-C. Finally, we show that the dronc promoter has BR-C interaction sites, and that it can be transactivated by a specific isoform of BR-C. These results indicate that BR-C plays a key role in ecdysone-mediated caspase regulation.
Cakouros
Dimitrios
D
Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, SA 5000, Australia.
Daish
Tasman
T
Martin
Damali
D
Baehrecke
Eric H
EH
Kumar
Sharad
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004330:Drosophila / Q000196:embryology / Q000378:metabolism*; D029721:Drosophila Proteins; D004440:Ecdysone / Q000494:pharmacology* / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000201:enzymology; D004790:Enzyme Induction; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D008675:Metamorphosis, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers
C102117:Br protein, Drosophila; D029721:Drosophila Proteins; D014157:Transcription Factors; D004440:Ecdysone; D020169:Caspases; C118731:dronc protein, Drosophila