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

Curr Biol. 1999 Mar 25;9(6):292-301. 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Apoptosis / physiology*
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins*
  • Caspase Inhibitors
  • Caspases / physiology
  • Cell Division / physiology*
  • Drosophila melanogaster / genetics
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / metabolism
  • Gene Expression Regulation, Developmental
  • Genes, Helminth*
  • Germ Cells / cytology
  • Helminth Proteins / antagonists & inhibitors
  • Helminth Proteins / genetics
  • Helminth Proteins / physiology*
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Mammals / genetics
  • Microtubule-Associated Proteins*
  • Molecular Sequence Data
  • Neoplasm Proteins
  • Proteins / genetics
  • Proteins / physiology
  • RNA, Double-Stranded / pharmacology
  • Recombinant Fusion Proteins / physiology
  • Saccharomyces cerevisiae / genetics
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Survivin
  • Transcription, Genetic / drug effects


  • BIRC5 protein, human
  • Caenorhabditis elegans Proteins
  • Caspase Inhibitors
  • Helminth Proteins
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Proteins
  • RNA, Double-Stranded
  • Recombinant Fusion Proteins
  • Survivin
  • bir-1 protein, C elegans
  • bir-2 protein, C elegans
  • Caspases