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Comments on Contreras, Vince et al. (2010) C. elegans: Development and Gene Expression, EMBL, Heidelberg, Germany "Multiple isoforms of translation factor IFG-1 induce germ cell apoptosis by a caspase-dependent mechanism in C. elegans" (0)
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Contreras, Vince, Henderson, Melissa A, Hao, Enhui, & Keiper, Brett D (2010). Multiple isoforms of translation factor IFG-1 induce germ cell apoptosis by a caspase-dependent mechanism in C. elegans presented in C. elegans: Development and Gene Expression, EMBL, Heidelberg, Germany. Unpublished information; cite only with author permission.
During apoptosis, the mammalian executioner protease caspase-3 cleaves the cellular protein synthesis initiation complex. Cleavage of the translation factor eIF4G results in the cap-independent synthesis of pro-apoptotic proteins such as Apaf-1. In the C. elegans gonad, apoptosis occurs naturally to selectively remove germ cells that will not mature as oocytes. We have demonstrated that worms express multiple isoforms of eIF4G from a single gene ( ifg-1 ). The isoforms of IFG-1 (p170 and p130) differ structurally and in their ability to associate with mRNA cap complexes. Here we show that like human eIF4G, IFG-1 p170 is a substrate for caspase-3 as well as its worm ortholog, CED-3. In addition, cleavage of IFG-1 separates the eIF4E binding site from the ribosome binding domain, indicating that a similar cap-independent program may be utilized during germ cell apoptosis. Coincidentally, the CED-3 cleavage site in p170 is adjacent to the translation start IFG-1 p130, suggesting that modification of the long IFG-1 isoform may mimic p130 function and sustain the apoptotic cascade. Expression of the Apaf-1 ortholog CED-4 and apoptosome formation are induced in dying germ cells in the absence of IFG-1 p170. Mutant worms lacking either ced-3 or ced-4 function showed complete suppression of germ cell death in ifg-1 p170 (RNAi) worms. While embryonic lethality was still observed in the F1s, as previously described, the number of mature oocytes was substantially rescued, suggesting non-apoptotic functional roles for the IFG-1 p130 that are utilized for late oogenesis. The data indicate that changes in protein synthesis mechanism alter the fate of germ cells by upstream activation o f the apoptotic cascade. A balance between p170 and p130 isoforms must be maintained to prevent the induction of CED-4 in order for oocytes to complete their developmental fate.