Human caspase-7 activity and regulation by its N-terminal peptide

J Biol Chem. 2003 Sep 5;278(36):34042-50. doi: 10.1074/jbc.M305110200. Epub 2003 Jun 24.


Central to the execution phase of apoptosis are the two closely related caspase-3 and -7. They share common substrate specificity and structure, but differ completely in the sequence of their respective N-terminal regions including their N-peptides, a 23-28 residue segment that are removed during zymogen activation. We show that the N-peptide of caspase-7 plays no role in the fundamental activation or properties of the active protease in vitro. However, the N-peptide modifies the properties of caspase-7 in vivo. In ectopic expression experiments, caspase-7 constructs with no N-peptide are far more lethal than constructs that have an uncleavable peptide. Moreover, the N-peptide of caspase-7 must be removed before efficient activation of the zymogen can occur in vivo. These disparate requirements for the N-peptide argue that it serves to physically sequester the caspase-7 zymogen in a cytosolic location that prevents access by upstream activators (caspase-8, -9, and -10). The N-peptide must first be removed, probably by caspase-3, before efficient conversion and activation of the zymogen can occur in vivo.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • COS Cells
  • Caspase 3
  • Caspase 7
  • Caspases / chemistry*
  • Caspases / metabolism*
  • Catalytic Domain
  • Cell Line
  • Cell Nucleus / enzymology
  • Cytosol / enzymology
  • DNA Fragmentation
  • DNA, Complementary / metabolism
  • Dimerization
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Immunoblotting
  • Kinetics
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Mutation
  • Peptides / chemistry
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Time Factors
  • Transfection


  • DNA, Complementary
  • Peptides
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • CASP3 protein, human
  • CASP7 protein, human
  • Caspase 3
  • Caspase 7
  • Caspases