Inhibition of actin polymerization enhances commitment to and execution of apoptosis induced by withdrawal of trophic support

S. Celeste Morley, Guang Ping Sun, Barbara E. Bierer

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

We have previously shown, using jasplakinolide, that stabilization of the actin cytoskeleton enhanced apoptosis induced upon cytokine withdrawal (Posey and Bierer [1999] J. Biol. Chem. 274:4259-4265). It remained possible, however, that a disruption in the regulation of actin dynamics, and not simply F-actin stabilization, was required to affect the transduction of an apoptotic signal. We have now tested the effects of cytochalasin D, a well-characterized agent that promoted actin depolymerization. Actin depolymerization did not affect CD95 (Fas)-induced death of Jurkat T cells in the time course studied but did enhance the commitment to cytokine withdrawal-induced apoptosis of factor-dependent cell lines. The induction of cell death was not the result of direct cytoskeletal collapse, since treatment of the cells with cytochalasin D in the presence of IL-2 did not promote death. As with jasplakinolide, the enhancement of commitment to apoptosis could be delayed by overexpression of the anti-apoptotic protein Bcl-XL, but, unlike jasplakinolide, cytochalasin D modestly affected the "execution" stage of apoptosis as well. Taken together, these results suggest that changes in actin dynamics, i.e., the rate of actin polymerization and depolymerization, modulate the transduction of the apoptotic signal committing lymphocytes, withdrawn from required growth factors, to the death pathway.

Original languageEnglish
Pages (from-to)1066-1076
Number of pages11
JournalJournal of cellular biochemistry
Volume88
Issue number5
DOIs
StatePublished - Apr 1 2003

Keywords

  • Actin
  • Apoptosis
  • Cytochalasin D
  • Cytokine-withdrawal

Fingerprint

Dive into the research topics of 'Inhibition of actin polymerization enhances commitment to and execution of apoptosis induced by withdrawal of trophic support'. Together they form a unique fingerprint.

Cite this