During the course of Drosophila metamorphosis, obsolete larval tissues are deleted through apoptosis. A single steroid hormone called ecdysone regulates this process. Pulses of ecdysone correlate with metamorphic stage progression. Ecdysone action also correlates to activation of Dronc, a caspase that is essential to ecdysone-induced cell death. The hormone binds to a heterodimeric receptor that regulates the transcription of other transcriptional regulators. Among these is Broad-Complex (BR-C), which in turn regulates secondary response genes. Cakouros et al. show that Dronc expression is regulated by BR-C in response to ecdysone in cultured Drosophila cells, as well as in fly larvae. Inhibition of BR-C expression in either system reduced both the expression of Dronc and apoptosis caused by the hormone. The study confirms that temporal regulation of transcription factors can control cell death machinery during development.
Inhibitors of apoptosis proteins (IAPs) block cell death by binding to caspases, and Drosophila IAP (DIAP1) regulates Dronc in this way. Wilson et al. report that the RING domain of DIAP is required to inhibit Dronc action. Mutation of the RING domain enhanced cell death in transgenic flies, a phenotype similar to that induced by Dronc overexpression. RING domains can function as E3 ubiquitin ligases, and the authors show that ubiquitination and degradation of both itself and Dronc depended on the RING finger of DIAP. This effect was dependent on DIAP interaction with Dronc. The study suggests that IAPs suppress apoptosis by targeting their associated caspases for degradation.
D. Cakouros, T. Daish, D. Martin, E. H. Baehrecke, S. Kumar, Ecdysone-induced expression of the caspase DRONC during hormone-dependent programmed cell death in Drosophila is regulated by Broad-Complex. J. Cell Biol. 157, 985-995 (2002). [Abstract] [Full Text]
R. Wilson, L. Goyal, M. Ditzel, A. Zachariou, D. A. Baker, J. Agapite, H. Steller, P. Meier, The DIAP1 RING finger mediates ubiquitination of DRONC and is indispensable for regulating apoptosis. Nature Cell Biol. 4, 445-450 (2002). [Online Journal]