Caspase-7 Gene Disruption Reveals an Involvement of the Enzyme during the Early Stages of Apoptosis

Nadia Korfali, Sandrine Ruchaud, David Loegering, Delphine Bernard, Colin Dingwall, Scott H. Kaufmann, William C. Earnshaw

Research output: Contribution to journalArticle

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Abstract

Caspases play a key role during apoptotic execution. In an attempt to elucidate the specific role of caspase-7 we generated a chicken DT40 cell line in which both alleles of the gene were disrupted. Viability assays showed that caspase-7-/- clones are more resistant to the common apoptosis-inducing drugs etoposide and staurosporine. Caspase-7-/- cells show a delay in phosphatidylserine externalization and DNA fragmentation as well as cleavage of the caspase substrates poly(ADP-ribose) polymerase 1 and lamins B1 and B2. Caspase affinity labeling and activity assays indicated that deficient cells exhibit a delay in caspase activation compared with wild type DT40 cells, providing an explanation for the differences in apoptotic execution between caspase-7 null and wild type DT40 cells. These results strongly suggest that caspase-7 is involved earlier than other effector caspases in the apoptotic execution process in DT40 B lymphocytes.

Original languageEnglish (US)
Pages (from-to)1030-1039
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number2
DOIs
StatePublished - Jan 9 2004

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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