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

Fraser, A. G., James, C., Evan, G. I., Hengartner, M. O. (March 1999) Caenorhabditis elegans inhibitor of apoptosis protein (IAP) homologue BIR-1 plays a conserved role in cytokinesis. Current Biology, 9 (6). pp. 292-301. ISSN 0960-9822 (Print)

DOI: 10.1016/S0960-9822(99)80137-7


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 approximately 70 amino-acid baculovirus IAP repeat (BIR), and this domain is essential for the anti-apoptotic activity of the IAPs. Both the marked structural diversity of IAPs and the identification of BIR-containing proteins (BIRPs) in yeast, however, 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, although its role at the spindle is still unclear. RESULTS: We have identified and characterised two Caenorhabditis elegans BIRPs,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 expression throughout other stages of development; bir-2 expression is detectable only in adults and embryos. Overexpression of bir-1 was unable to inhibit developmentally occurring cell death in C. elegans and inhibition of bir-1 expression did not increase cell death. Instead, embryos lacking bir-1 were unable to complete cytokinesis and they became multinucleate. This cytokinesis defect could be partially suppressed by transgenic expression of survivin, the mammalian BIRP most structurally related to BIR-1, suggesting a conserved role for BIRPs in the regulation of cytokinesis. CONCLUSIONS: BIR-1, a C. elegans BIRP, is probably not involved in the general regulation of apoptosis but is required for embryonic cytokinesis. We suggest that BIRPs may regulate cytoskeletal changes in diverse biological processes including cytokinesis and apoptosis.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Animals Animals, Genetically Modified Apoptosis/ physiology Caenorhabditis elegans/embryology/genetics/growth & development/ physiology Caenorhabditis elegans Proteins Caspases/antagonists & inhibitors/physiology Cell Division/ physiology Comparative Study Drosophila melanogaster/genetics Embryo, Nonmammalian/cytology/metabolism Gene Expression Regulation, Developmental Genes, Helminth Germ Cells/cytology Helminth Proteins/antagonists & inhibitors/genetics/ physiology Humans Mammals/genetics Microtubule-Associated Proteins Molecular Sequence Data Neoplasm Proteins Proteins/genetics/physiology RNA, Double-Stranded/pharmacology Recombinant Fusion Proteins/physiology Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Saccharomyces cerevisiae/genetics Sequence Alignment Sequence Homology, Amino Acid Species Specificity Transcription, Genetic/drug effects
Subjects: bioinformatics > genomics and proteomics > design > amino acid design
organism description > animal > C elegans
diseases & disorders > neoplasms
organism description > yeast > Saccharomyces
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > Protease > caspases
organism description > animal > developmental stage > embryo
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
CSHL Authors:
Communities: CSHL labs > Hengartner lab
Depositing User: Kathleen Darby
Date: 25 March 1999
Date Deposited: 28 Apr 2014 15:41
Last Modified: 30 Apr 2014 17:43
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