Involvement of CD45 in DNA fragmentation in apoptosis induced by mitochondrial perturbing agents

Apoptosis. 2008 Feb;13(2):197-212. doi: 10.1007/s10495-007-0162-9.


CD45 is a type I transmembrane molecule with phosphatase activity which comprises up to 10% of the cell surface area in nucleated haematopoietic cells. We have previously demonstrated the absence of nuclear apoptosis in CD45-negative T cells after chemical-induced apoptosis. The aim of this study was to characterize the role of CD45 in nuclear apoptosis. In contrast to wild type CD45-positive T cells, the CD45-deficient T cell lines are resistant to the induction of DNA fragmentation and chromatin condensation following tributyltin (TBT) or H2O2 exposure, but not to cycloheximide-induced apoptosis. CD45 transfection in deficient cell lines led to the restoration of chromatin condensation and DNA fragmentation following TBT exposure. In both CD45-positive and negative T cell lines, TBT exposure mediates intracellular calcium mobilization, caspase-3 activation and DFF45 cleavage. Moreover, DNA fragmentation was also induced by TBT in cells deficient in expression of p56lck, ZAP-70 and SHP-1. Subcellular partitioning showed a decrease in nuclear localisation of caspase-3 and DFF40. Together, these results demonstrate for the first time, that CD45 expression plays a key role in internucleosomal DNA fragmentation and chromatin condensation processes during apoptosis. CD45 activity or its substrates' activity, appears to be located downstream of caspase-3 activation and plays a role in retention of DFF40 in the nucleus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Calcium / metabolism
  • Caspase 3 / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cytochromes c / metabolism
  • Cytoplasm / metabolism
  • DNA Fragmentation / drug effects*
  • Deoxyribonucleases / metabolism*
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Leukocyte Common Antigens / deficiency
  • Leukocyte Common Antigens / genetics
  • Leukocyte Common Antigens / metabolism*
  • Membrane Potential, Mitochondrial
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Poly-ADP-Ribose Binding Proteins
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / metabolism
  • Transfection
  • Trialkyltin Compounds / pharmacology*


  • Poly-ADP-Ribose Binding Proteins
  • Trialkyltin Compounds
  • tributyltin
  • Cytochromes c
  • Hydrogen Peroxide
  • DFFB protein, human
  • Deoxyribonucleases
  • Leukocyte Common Antigens
  • Caspase 3
  • Calcium