Drosophila sickle Is a Novel grim-reaper Cell Death Activator

Abstract

The Drosophila genes reaper, head involution defective (hid), and grim all reside at 75C on chromosome three and encode related proteins that have crucial functions in programmed cell death (reviewed in ). In this report, we describe a novel grim-reaper gene, termed sickle, that resides adjacent to reaper. The sickle gene, like reaper and grim, encodes a small protein which contains an RHG motif and a Trp-block. In wild-type embryos, sickle expression was detected in cells of the developing central nervous system. Unlike reaper, hid, and grim, the sickle gene is not removed by Df(3L)H99, and strong ectopic sickle expression was detected in the nervous system of this cell death mutant. sickle very effectively induced cell death in cultured Spodoptera Sf-9 cells, and this death was antagonized by the caspase inhibitors p35 or DIAP1. Strikingly, unlike the other grim-reaper genes, targeted sickle expression did not induce cell death in the Drosophila eye. However, sickle strongly enhanced the eye cell death induced by expression of either an r/grim chimera or reaper.

Maternal Nanos represses hid / skl -dependent apoptosis to maintain the germ line in Drosophila embryos

“…These proteins share a common motif at their N terminus (55). This motif, referred to as the RHG motif, is essential for the ability of RHG proteins to induce apoptosis (49). The RHG motif interacts with the BIR (baculovirus IAP repeat) domain of Diap1 (Drosophila inhibitor of apoptosis protein 1) to oppose BIR-mediated caspase inhibition (56).…”

“…Critical regulators of apoptosis function by antagonizing inhibitor of apoptosis protein (IAP) that directly blocks caspase action (40,41). In Drosophila, four proapoptotic genes, reaper (rpr), head involution defective (hid), grim, and sickle (skl), encode members of a family of related proteins that bind to and inactivate the IAP (42)(43)(44)(45)(46)(47)(48)(49). They are also referred to as RHG genes.…”

Dissection of DIAP1 Functional Domains via a Mutant Replacement Strategy

“…Binding of IBM proteins to the IAP BIR domains blocks the caspase inhibitory function of the IAP (8, 10 -12). In Drosophila, the IBM-containing proteins Reaper (Rpr), Hid, Grim, and Sickle bind Drosophila IAP1 (DIAP1) (9,(13)(14)(15)(16). Rpr, Hid, and Grim act together to regulate most developmental apoptosis (17).…”

A Bax/Bak-independent Mitochondrial Death Pathway Triggered by Drosophila Grim GH3 Domain in Mammalian Cells

“…Studies in the fly Drosophila melanogaster have uncovered four essential components of the genetic program controlling cell death, reaper, hid, sickle, and grim, whose transcriptional activation precedes, induces and is necessary for programmed cell death by apoptosis (7)(8)(9)(10)(11)(12). The four genes map to a single genetic complex and function as death switches that are regulated mainly at the transcriptional level, although Hid is also regulated through phosphorylation by the mitogen-activated protein kinase pathway (13,14).…”