The proteasome regulates caspase-dependent and caspase-independent protease cascades during apoptosis of MO7e hematopoietic progenitor cells

Wu Li-Wha, Suzanna Reid, Alec Ritchie, Hal Broxmeyer, David B. Donner

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Withdrawal of trophic support from growth factor-dependent MO7e human myeloid progenitor cells induces apoptosis characterized by DNA fragmentation and degradation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). Inhibitors of caspase (ICE) protease family members did not inhibit apoptosis or DNA fragmentation induced by factor withdrawal, but blocked degradation of DNA-PKcs. Thus, caspase activity accounts for only a component of the apoptotic program in MO7e hematopoietic cells. The protease inhibitor TPCK, but not other protease inhibitors, blocked DNA fragmentation, but not degradation of DNA-PKcs during apoptosis of MO7e cells. Thus, caspase-independent and caspase-dependent protease cascades mediate distinct features of MO7e cell apoptosis. The proteasome inhibitors calpain inhibitor I and lactacystin promoted DNA fragmentation, degradation of DNA-PKcs and apoptosis of MO7e cells. The ability of lactacystin to promote DNA fragmentation was abrogated by TPCK, but not by caspase inhibitors, whereas the ability of lactacystin to promote degradation of DNA-PKcs was blocked by caspase inhibitors, but not by TPCK. Thus, caspase-dependent and caspase- independent protease cascades are downstream of and regulated by the proteasome, which plays a central role in regulating the multiple protease cascades that induce apoptosis.

Original languageEnglish
Pages (from-to)20-29
Number of pages10
JournalBlood Cells, Molecules and Diseases
Volume25
Issue number1
DOIs
StatePublished - Feb 1999

Fingerprint

Proteasome Endopeptidase Complex
Caspases
Hematopoietic Stem Cells
DNA Fragmentation
Tosylphenylalanyl Chloromethyl Ketone
Peptide Hydrolases
Apoptosis
Caspase Inhibitors
Protease Inhibitors
DNA
Aptitude
DNA-Activated Protein Kinase
Catalytic DNA
Myeloid Progenitor Cells
Proteasome Inhibitors
Catalytic Domain
Intercellular Signaling Peptides and Proteins
lactacystin

Keywords

  • Cell death
  • DNA fragmentation
  • Factor withdrawal

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine
  • Hematology

Cite this

The proteasome regulates caspase-dependent and caspase-independent protease cascades during apoptosis of MO7e hematopoietic progenitor cells. / Li-Wha, Wu; Reid, Suzanna; Ritchie, Alec; Broxmeyer, Hal; Donner, David B.

In: Blood Cells, Molecules and Diseases, Vol. 25, No. 1, 02.1999, p. 20-29.

Research output: Contribution to journalArticle

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