Characterization of Two C. Elegans Homologuses of Oncogenic Inhibitor of Apoptosis Proteins (IAPs) and Identification of Interacting Genes
Abstract
Inhibitor of Apoptosis Proteins (IAPs) suppress apoptosis both in the fruit fly Drosophila melanogaster and in vertebrates. All IAPs contain at least a single copy of a highly conserved domain, the Baculovirus IAP Repeat (BIR) domain; this is essential for their anti-apoptotic activity. Understanding how a BIR domain regulates apoptosis is thus an important step in furthering our understanding of the molecular mechanisms of apoptosis. I have previously identified two BIR-containing Proteins (BIRPs) in the nematode worm C. elegans. One of these, BIR-l, appears to play no role in the regulation of programmed cell death in C. elegans; however, BIR-l is required for the completion of cytokinesis. Cytokinesis is a complex process that is likely to be highly regulated and to involve a large number of proteins. My approach to understanding how BIR-l functions in cytokinesis has been to try to identify other genes that are also required for cytokinesis in C. ejegans and subsequently to attempt to understand how BIR-l relates to this machinery. Rather than examine individual candidate genes to determine whether they have a role in cytokinesis, I wished to carry out a genome-wide screen to identify all genes that are required for cytokinesis; to do this I have made use of RNA-mediated inhibition (RNAi). RNAi is a technique whereby the activity of a particular gene is transiently inhibited following the introduction of dsRNA of sequence specific to the targeted gene. The specificity and potency of RNAi make it an ideal technique to investigate gene function beginning only with genomic sequence. I have screened 90% of genes on Chromosome I of C. elegans for RNAi phenotypes and have identified S genes which have a similar RNAi phenotype to BIR-l. I aim to extend this to appraoch over the entire genome in the coming year and thence to spend time characterizing genes found to be required for cytokinesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA390410
Entities
People
- Andrew Fraser
- Julie Ahringer
Organizations
- University of Cambridge