Caspase activation and apoptosis in response to proteasome inhibitors

C. J. Henderson, E. Aleo, A. Fontanini, R. Maestro, G. Paroni, C. Brancolini

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

Several studies have indicated that proteasome inhibitors (PIs) are promising anticancer agents. We have discovered that PIs have the unique ability to activate effector caspases through a mitochondrial Bcl-2 inhibitable but caspase-9 independent pathway. Stabilization of released Smac induced by blockade of the proteasome could explain the apoptosome-independent cell death induced by PIs. Infact, Smac/DIABLO critically supports this PIs-dependent caspase activation. By using a new assay, we confirm that at a single cell level both Smac and PIs can activate caspases in the absence of the apoptosome. Moreover, we have observed two PIs-induced kinetics of caspase activation, with caspase-9 being still required for the rapid caspase activation in response to mitochondrial depolarization, but dispensable for the slow DEVDase activation. In summary, our data indicate that PIs can activate downstream caspases at least in part through Smac/DIABLO stabilization.

Original languageEnglish
Pages (from-to)1240-1254
Number of pages15
JournalCell Death and Differentiation
Volume12
Issue number9
DOIs
Publication statusPublished - Sep 2005

Fingerprint

Proteasome Inhibitors
Caspases
Apoptosis
Apoptosomes
Caspase 9
Effector Caspases
Proteasome Endopeptidase Complex
Antineoplastic Agents
Cell Death

Keywords

  • Caspase
  • Chemotherapy
  • GFP
  • IAP
  • Mitochondria
  • Time lapse
  • TMRM

ASJC Scopus subject areas

  • Cell Biology

Cite this

Henderson, C. J., Aleo, E., Fontanini, A., Maestro, R., Paroni, G., & Brancolini, C. (2005). Caspase activation and apoptosis in response to proteasome inhibitors. Cell Death and Differentiation, 12(9), 1240-1254. https://doi.org/10.1038/sj.cdd.4401729

Caspase activation and apoptosis in response to proteasome inhibitors. / Henderson, C. J.; Aleo, E.; Fontanini, A.; Maestro, R.; Paroni, G.; Brancolini, C.

In: Cell Death and Differentiation, Vol. 12, No. 9, 09.2005, p. 1240-1254.

Research output: Contribution to journalArticle

Henderson, CJ, Aleo, E, Fontanini, A, Maestro, R, Paroni, G & Brancolini, C 2005, 'Caspase activation and apoptosis in response to proteasome inhibitors', Cell Death and Differentiation, vol. 12, no. 9, pp. 1240-1254. https://doi.org/10.1038/sj.cdd.4401729
Henderson, C. J. ; Aleo, E. ; Fontanini, A. ; Maestro, R. ; Paroni, G. ; Brancolini, C. / Caspase activation and apoptosis in response to proteasome inhibitors. In: Cell Death and Differentiation. 2005 ; Vol. 12, No. 9. pp. 1240-1254.
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