Caspase-mediated proteolysis during apoptosis: Insights from apoptotic neutrophils

Darshak M. Sanghavi, Marcus Thelen, Nancy A. Thornberry, Livia Casciola-Rosen, Antony Rosen

Research output: Contribution to journalArticlepeer-review

Abstract

Apoptosis is initiated by activation of caspases (interleukin 1β-converting enzyme homologues), which cause coordinated cleavage of several death substrates that function in structural or homeostatic pathways. The relationship between substrate cleavage and apoptosis is not yet known, nor is it clear whether cleavage of specific substrates is a critical requirement for apoptosis. The human neutrophil provides novel insights into the roles of proteolysis of specific substrates during apoptosis, since only a subset of caspase substrates are present in mature neutrophils. Of the death substrates we screened, PARP, the nuclear mitotic apparatus protein (NuMA), the 70 kDa subunit of the U1 small ribonucleoprotein (U1-70kDa) and the catalytic subunit of DNA-dependent protein kinase (DNA-PK(CS)) were not detected in non-apoptotic neutrophils; in contrast, lamin B and fodrin were present in amounts similar to those found in other cells. Caspase-3 activity was absent in freshly isolated neutrophils, but was detected when neutrophils mere aged in vitro, coincident with the onset of morphologic and biochemical apoptosis. The absence of PARP, NUMA, U1-70kDa and DNA-PK(CS) in non-apoptotic neutrophils suggests that these are not critical anti-npoptotic proteins, and that their fragments are not required components of the neutrophil apoptotic pathway. These studies highlight the conserved role of caspase activation in the apoptotic mechanism, and focus attention on several conserved structural substrates as potential transducers of the proteolytic signal in apoptosis.

Original languageEnglish (US)
Pages (from-to)179-184
Number of pages6
JournalFEBS Letters
Volume422
Issue number2
DOIs
StatePublished - Jan 30 1998

Keywords

  • Apoptosis
  • Caspase
  • Proteolysis

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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