Abstract MULTIPLE TRANSLATION FACTOR eIF4G (IFG-1) ISOFORMS ARE REQUIRED FOR THE APOPTOSOME-DEPENDENT ACTIVATION OF GERM CELL APOPTOSIS

Apoptosis is a naturally occurring process during animal development required for the programmed killing and removal of injured cells. Cellular insult induces a switch in translation that allows for the rapid synthesis of proteins that quickly destroy the unhealthy cell and remove it from undamaged tissue. In mammalian cells, this selective modulation of translation has been attributed to modifications of the protein synthesis machinery by apoptotic caspases. Specifically the initiation complex scaffold protein eIF4G becomes cleaved to disrupt cap-dependent translation and induce the IRES-dependent synthesis of apoptogenic mRNAs like Apaf-1. While the biochemistry of these cleavage events has been well characterized, how disruptions in translation mechanism affect apoptotic signaling still remains largely unknown. The nematode Caenorhabditis elegans was used to study how the balance between cap-dependent and –independent translation mechanisms mediate the translation of pro-apoptotic Apaf-1/CED-4 to alter the fate of healthy germ cells. Two major eIF4G (IFG-1) isoforms, derived from a single gene, were found to be broadly expressed throughout all stages of development. IFG-1 p170 and p130 appeared to both associate with ribosomes yet differed in their N-termini. Analysis of mRNA cap complexes showed that only IFG-1 p170 associates with C. elegans eIF4Es (IFEs