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J. Cell Biol. 157 (6): 985-996

Copyright © 2002 by the Rockefeller University Press.

Article

Ecdysone-induced expression of the caspase DRONC during hormone-dependent programmed cell death in Drosophila is regulated by Broad-Complex

Dimitrios Cakouros1, Tasman Daish1,2, Damali Martin3, Eric H. Baehrecke3, and Sharad Kumar1,2

1 Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Adelaide, SA 5000, Australia
2 Department of Medicine, Adelaide University, Adelaide, SA 5005, Australia
3 University of Maryland Biotechnology Institute, College Park, MD 20742

Address correspondence to Sharad Kumar, Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, P.O. Box 14, Rundle Mall, Adelaide, SA 5000, Australia. Tel.: 61-8-8222-3738. Fax: 61-8-8222-3139. E-mail: asharad.kumar{at}imvs.sa.gov.au

Abstract: 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.

Key Words: hormone; apoptosis; BR-C; RNAi; transcription

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