Deterin, a new inhibitor of apoptosis from Drosophila melanogaster

Deterin, a new apoptosis inhibitor from Drosophila melanogaster, possesses an unusual structure of only a single baculovirus inhibitor of apoptosis (L AP)-type repeat and no RING finger motif. The biochemical actions of deteri n are demonstrated in SF9 and S2 cell transfection assays, in which the exp ressed protein acts in the cytoplasm to inhibit or deter cells from apoptos is otherwise induced by the caspase-dependent apoptosis activator reaper or by cytotoxicants, A loss of function phenotype for deterin of cell death w as indicated by transfections with either a dominant negative deterin mutan t or with inhibitory RNA (RNAi) for deterin, The dominant negative C-termin al fragment that antagonized antiapoptotic activity of deterin did not affe ct antiapoptotic activity of DIAP1 or p35. Both the baculovirus IAP-type re peat (BIR) domain and the alpha-helical C-terminal domain are necessary in both SF9 and 52 cells for deterin to manifest its activity to prevent cell death. The approximately 650-base deterin transcript is present in embryos, third instar larvae, acid late stage nurse cells of adult females. The det erin transcript is distributed throughout early stage embryos, whereas in l ater stage embryos it becomes progressively restricted to the central nervo us system and gonads. Whereas the nematode survivin-type ZAP has thus far b een implicated only as a mitotic regulator, Drosophila deterin constitutes the first invertebrate member of the sunvivin-type IAP group to exhibit apo ptosis-inhibitory activity.