DFF, a Heterodimeric Protein That Functions Downstream of caspase-3 to Trigger DNA Fragmentation During Apoptosis

Cell. 1997 Apr 18;89(2):175-84. doi: 10.1016/s0092-8674(00)80197-x.

Abstract

We have identified and purified from HeLa cytosol a protein that induces DNA fragmentation in coincubated nuclei after it is activated by caspase-3. This protein, designated DNA Fragmentation Factor (DFF), is a heterodimer of 40 kDa and 45 kDa subunits. The amino acid sequence of the 45 kDa subunit, determined from its cDNA sequence, reveals it to be a novel protein. Caspase-3 cleaves the 45 kDa subunit at two sites to generate an active factor that produces DNA fragmentation without further requirement for caspase-3 or other cytosolic proteins. In cells undergoing apoptosis, the 45 kDa subunit is cleaved in the same pattern as it is cleaved by caspase-3 in vitro. These data delineate a direct signal transduction pathway during apoptosis: caspase-3 to DFF to DNA fragmentation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis / physiology
  • Caspase 3
  • Caspases*
  • Cell Line
  • Cloning, Molecular
  • Cricetinae
  • Cysteine Endopeptidases / metabolism*
  • Cytosol / chemistry
  • DNA Fragmentation*
  • DNA, Complementary / genetics
  • Dimerization
  • HeLa Cells / chemistry
  • Humans
  • Lamins
  • Liver
  • Molecular Sequence Data
  • Molecular Weight
  • Monocytes / cytology
  • Nuclear Proteins / metabolism
  • Proteins / chemistry
  • Proteins / genetics
  • Proteins / isolation & purification*
  • Proteins / metabolism
  • Proteins / physiology*
  • Sequence Analysis
  • Signal Transduction / physiology

Substances

  • DNA fragmentation factor, human
  • DNA, Complementary
  • Lamins
  • Nuclear Proteins
  • Proteins
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases

Associated data

  • GENBANK/U91985