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. hormone; apoptosis; BR-C; RNAi; transcription Footnotes ↵ * Abbreviations used in this paper: BR-C, Broad-Complex; dsRNA, double-stranded RNA; EMSA, electrophoretic mobility shift analysis; FKH, Fork Head; RNAi, RNA interference. Submitted: 8 January 2002 Accepted: 29 April 2002 Revision received 26 April 2002
The Journal of Cell Biology – Rockefeller University Press
Published: Jun 10, 2002
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