Control of the cell death pathway by Dapaf-1, a Drosophila Apaf-1/CED-4-related caspase activator

Mol Cell. 1999 Nov;4(5):757-69. doi: 10.1016/s1097-2765(00)80386-x.

Abstract

We identified a Drosophila Apaf-1/CED-4 homolog gene, dapaf-1. Alternative splicing results in two dapaf-1 mRNA species, which encode distinct forms of caspase activator, Dapaf-1L (Apaf-1 type) and Dapaf-1S (CED-4 type). Distinct caspases were activated by these Dapaf-1 isoforms. Loss of Dapaf-1 function resulted in defective cytochrome c-dependent caspase activities and reduced apoptosis in embryo and in larval brain. Dapaf-1 activities were also involved in cell death induced by ectopic expression of reaper in the compound eye. These data suggest that Dapaf-1/cytochrome c-dependent cell death-inducing machinery is present in Drosophila, and the requirement of Dapaf-1/Apaf-1 in neural cell death is conserved through evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Apoptosis*
  • Apoptotic Protease-Activating Factor 1
  • Base Sequence
  • Brain / cytology
  • Brain / embryology
  • Brain / metabolism
  • Caenorhabditis elegans Proteins*
  • Calcium-Binding Proteins / chemistry*
  • Calcium-Binding Proteins / genetics
  • Caspases / chemistry
  • Caspases / metabolism*
  • Cell Line
  • Cloning, Molecular
  • Cytochrome c Group / metabolism
  • Drosophila Proteins*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / embryology
  • Drosophila melanogaster / enzymology
  • Drosophila melanogaster / genetics
  • Enzyme Activation
  • Evolution, Molecular
  • Eye / cytology
  • Eye / metabolism
  • Helminth Proteins / chemistry*
  • Helminth Proteins / genetics
  • Larva / cytology
  • Larva / metabolism
  • Molecular Sequence Data
  • Mutation / genetics
  • Peptides / genetics
  • Peptides / physiology
  • Protein Binding
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Proteins / chemistry*
  • Proteins / genetics
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Sequence Homology, Amino Acid

Substances

  • Apoptotic Protease-Activating Factor 1
  • Caenorhabditis elegans Proteins
  • Calcium-Binding Proteins
  • Ced-4 protein, C elegans
  • Cytochrome c Group
  • Drosophila Proteins
  • Helminth Proteins
  • Peptides
  • Protein Isoforms
  • Proteins
  • RNA, Messenger
  • rpr protein, Drosophila
  • Caspases

Associated data

  • GENBANK/AB027531
  • GENBANK/AB027532