Apaf-1, a Human Protein Homologous to C. Elegans CED-4, Participates in Cytochrome C-Dependent Activation of caspase-3

Cell. 1997 Aug 8;90(3):405-13. doi: 10.1016/s0092-8674(00)80501-2.

Abstract

We report here the purification and cDNA cloning of Apaf-1, a novel 130 kd protein from HeLa cell cytosol that participates in the cytochrome c-dependent activation of caspase-3. The NH2-terminal 85 amino acids of Apaf-1 show 21% identity and 53% similarity to the NH2-terminal prodomain of the Caenorhabditis elegans caspase, CED-3. This is followed by 320 amino acids that show 22% identity and 48% similarity to CED-4, a protein that is believed to initiate apoptosis in C. elegans. The COOH-terminal region of Apaf-1 comprises multiple WD repeats, which are proposed to mediate protein-protein interactions. Cytochrome c binds to Apaf-1, an event that may trigger the activation of caspase-3, leading to apoptosis.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptotic Protease-Activating Factor 1
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins*
  • Calcium-Binding Proteins / metabolism
  • Caspase 3
  • Caspases*
  • Cell Line
  • Cloning, Molecular
  • Cysteine Endopeptidases / biosynthesis
  • Cysteine Endopeptidases / metabolism*
  • Cytochrome c Group / metabolism*
  • Cytosol / metabolism
  • DNA, Complementary
  • Enzyme Activation
  • Enzyme Precursors / metabolism
  • HeLa Cells
  • Helminth Proteins / metabolism
  • Humans
  • Molecular Sequence Data
  • Proteins / chemistry*
  • Proteins / isolation & purification
  • Proteins / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transfection

Substances

  • APAF1 protein, human
  • Apoptotic Protease-Activating Factor 1
  • Caenorhabditis elegans Proteins
  • Calcium-Binding Proteins
  • Ced-4 protein, C elegans
  • Cytochrome c Group
  • DNA, Complementary
  • Enzyme Precursors
  • Helminth Proteins
  • Proteins
  • Recombinant Proteins
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases

Associated data

  • GENBANK/AF013263