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

J Cell Biol. 2002 Jun 10;157(6):985-95. doi: 10.1083/jcb.200201034. Epub 2002 Jun 3.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Caspases / genetics
  • Caspases / metabolism*
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Drosophila / embryology
  • Drosophila / metabolism*
  • Drosophila Proteins*
  • Ecdysone / pharmacology*
  • Ecdysone / physiology
  • Embryo, Nonmammalian / enzymology
  • Enzyme Induction
  • Gene Expression Regulation, Developmental
  • Gene Expression Regulation, Enzymologic
  • Metamorphosis, Biological
  • Molecular Sequence Data
  • Mutation
  • Promoter Regions, Genetic
  • Transcription Factors / genetics*
  • Zinc Fingers

Substances

  • Br protein, Drosophila
  • Drosophila Proteins
  • Transcription Factors
  • Ecdysone
  • Caspases
  • dronc protein, Drosophila