Caenorhabditis elegans inhibitor of apoptosis protein (IAP) homologue BIR-1 plays a conserved role in cytokinesis

Background: Inhibitor of apoptosis proteins (IAPs) suppress apoptotic cell death in several model systems and are highly conserved between insects and mammals. All IAPs contain at least one copy of the similar to 70 amino-aci d baculovirus IAP repeat (BIR), and this domain is essential for the anti-a poptotic activity of the IAPs. Both the marked structural diversity of IAPs and the identification of BIR-containing proteins (BIRPs) in yeast, howeve r, have led to the suggestion that: BIRPs might play roles in other, as yet unidentified, cellular processes besides apoptosis. Survivin, a human BIRP , is upregulated 40-fold at G2-M phase and binds to mitotic spindles, altho ugh its role at the spindle is still unclear. Results: We have identified and characterised two Caenorhabditis elegans BI RPs, BIR-1 and BIR-2; these proteins are the only BIRPs in C. elegans. The bir-1 gene is highly expressed during embryogenesis with detectable express ion throughout other stages of development; bir-2 expression is detectable only in adults and embryos. Overexpression of bir-1 was unable to inhibit d evelopmentally occurring cell death in C. elegans and inhibition of bir-1 e xpression did not increase cell death. Instead, embryos lacking bir-1 were unable to complete cytokinesis and they became multinucleate. This cytokine sis defect could be partially suppressed by transgenic expression of surviv in, the mammalian BIRP most structurally related to BIR-1,suggesting a cons erved role for BIRPs in the regulation of cytokinesis. Conclusions: BIR-1, a C. elegans BIRP, is probably not involved in the gene ral regulation of apoptosis but is required for embryonic cytokinesis. We s uggest that BIRPs may regulate cytoskeletal changes in diverse biological p rocesses including cytokinesis and apoptosis.