Source: http://cegg.unige.ch/insecta/immunodb

CASPAs: Caspase Activators
Summary

Bart Bryant and Rollie Clem 

Division of Biology, Kansas State University, Rollie Clem Lab, Ackert Hall, Manhattan, KS 66506-4901 

Caspase activators include ARK (Apaf-1 Related Killer) and IAP (Inhibitor of Apoptosis) antagonists. Only a single ARK homolog is present in each species, while multiple IAP antagonist genes are present per species. ARK proteins contain a CARD domain and an NB-ARC domain followed by multipleWD-40 domains, while IAP antagonists share only a small amino-terminal domain called IBM (IAP Binding Motif). In Drosophila, ARK binds to the initiator caspase Dronc and this complex is involved in forming the apoptosome, which is required for caspase activation. IAP antagonists interfere with the ability of IAP proteins to inhibit caspases. The best-studied IAP antagonist in Drosophila is reaper (rpr). The best model for interaction between IAPs and IAP antagonists is between rpr and DIAP1, which has been determined by both biochemical and genetic means (Hay and Guo. Annu. Rev. Cell. Dev. Biol. 2006). 

ARK has been characterized in Drosophila extensively (Zhou L et al. Mol Cell. 1999, Rodriguez A et al. Nat. Cell Biol. 1999, Kanuka H et al. Mol. Cell. 1999) and this gene has been recently cloned in Aedes aegypti (Bryant B et al. IBMB 2008). Using Aedes aegypti ARK as a query in BLAST against the Culex genome, we found regions of homology in supercontig 46. GenScan predictions match the domains found in Aedes aegypti ARK, so the gene model was considered valid. 

IAP antagonists were initially found in Drosophila in a developmental screen (White K. Science. 1994) and are represented below. In Drosophila these proteins share almost no homology except for the IBM. The first mosquito IAP antagonist was reported by Lei Zhou (Zhou L et al. EMBO reports. 2005) and is called Michelob_x. This gene is found in multiple mosquitoes and is represented below. The Aedes aegypti genome contains an additional IBM-containing gene called IMP (IAP antagonist Michelob_x-like Protein) and this gene has been shown to have pro-apoptotic activity (Bryant B et al. IBMB 2008). IMP was used as a BLAST query against the Culex genome and gene prediction was performed using GenScan. The resulting gene has relatively high identity for an IAP antagonist gene. Pro-apoptotic activity still needs to be tested to determine the validity of the gene model.