We have identified two genes from the C. elegans sequence database,
iap-1 and
iap-2, that encode predicted proteins with sequence similarity to the inhibitor-of-apoptosis proteins (IAPs). IAPs have previously been identified in baculoviruses, Drosophila, and mammals. All members of the IAP family contain at least one N-terminal baculoviral iap repeat (BIR), and some but not all members also contain a C-terminal C3HC4 RING finger. C. elegans IAP-1 contains two N-terminal BIRS, while IAP-2 contains one; neither IAP-1 nor IAP-2 contains a C-terminal RING finger. Many but not all members of the IAP family can block programmed cell death when overexpressed(1), suggesting that these IAPs may interact with a conserved member of the cell-death pathway. The normal cellular functions of Drosophila and mammalian IAPs, as well as the mechanism by which IAPs affect programmed cell death when overexpressed, however, remain to be determined. To understand better the functions of C. elegans iaps, we plan to characterize their loss-of-function and overexpression phenotypes as well as their protein and RNA expression patterns. Both iap genes are located on LG V;
iap-1 is between
gut-2 and
him-5, and
iap-2 is between
deg-3 and
daf-11. We have isolated full-length SL1 trans-spliced cDNAs for both genes. Embryos from N2 or
ced-3 mothers injected with
iap-2 antisense RNA arrest during early embryogenesis, suggesting that the arrest may not be
ced-3 dependent and may not be caused by ectopic programmed cell death. Based on this phenotype, we will seek mutations in
iap-2 by screening for lethal mutations that map to the
iap-2 region. We will also directly seek null alleles of
iap-1 by Tc1 mediated gene disruption. Finally, we are conducting 2-hybrid screens with both
iap-1 and
iap-2 to identify interacting proteins that may elucidate the biochemical pathways in which these molecules act. 1. Clem et al., Death and Differentiation 3:9-16, 1996