Diverse domains of THREAD/DIAP1 are required to inhibit apoptosis induced by REAPER and HID in drosophila

Significant amounts of apoptosis take place during Drosophila development. The proapoptotic genes reaper (rpr), grim, and head involution defective (h id) are required for virtually all embryonic apoptosis. The proteins encode d by these genes share a short region of homology at their amino termini. T he Drosophila WP homolog THREAD/DIAP1 (TH/DIAP1), encoded by the threat (th ) gene, negatively regulates apoptosis during development. It has been prop osed that RPR, GRIM, and HID induce apoptosis by binding and inactivating T H/DIAP1. The region of homology between the three proapoptotic proteins has been proposed to bind to the conserved BIR2 domain of TH/DIAP1. Here, we p resent an analysis of loss-of-function and grain-of-function alleles of th, which indicates that additional domains of TH/DIAP1 are necessary for its ability to inhibit death induced by RPR, GRIM, and HID. In addition, that a nalysis of loss-of-function mutations demonstrates that th is necessary to block apoptosis very early in embryonic development. This may reflect a req uirement to block maternally provided RPR and HID, or it may indicate anoth er function of the TH/DIAP1 protein.