Granzyme B/perforin-mediated apoptosis of Jurkat cells results in cleavage of poly(ADP-ribose) polymerase to the 89-kDa apoptotic fragment and less abundant 64-kDa fragment

Biochem Biophys Res Commun. 1996 Oct 23;227(3):658-65. doi: 10.1006/bbrc.1996.1565.


Cytotoxic lymphocytes utilize granule associated serine proteases (granzymes) and perforin to induce apoptosis. Although the importance of granzyme B has been established by gene ablation experiments, biochemical events initiated by the granzyme remain enigmatic. We show here that exposure of Jurkat cells to granzyme B and perforin results in cleavage of poly(ADP-ribose) polymerase to an apoptotic 89 kDa fragment and to lesser amounts of a 64 kDa fragment. The 64 kDa fragment is produced directly by granzyme B while the 89 kDa fragment is presumably generated by activated ICE/Ced-3 proteases. Establishing the intracellular function of GrB in the apoptotic response, these results indicate that granzyme B enters perforin treated targets activating the ICE/Ced-3 family proteases which then cleave poly(ADP-ribose) polymerase to its apoptotic fragment. Intracellular granzyme B appears to be translocated to the nucleus where the protease directly cleaves poly(ADP-ribose) polymerase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Cell-Free System
  • Granzymes
  • Humans
  • Hydrolysis
  • Jurkat Cells
  • Membrane Glycoproteins / metabolism*
  • Peptide Fragments / biosynthesis*
  • Perforin
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Pore Forming Cytotoxic Proteins
  • Serine Endopeptidases / metabolism*


  • Membrane Glycoproteins
  • Peptide Fragments
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • Poly(ADP-ribose) Polymerases
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases