Dissociation of apoptosis and activation of IL-1β-converting enzyme/ced-3 proteases by ALG-2 and the truncated Alzheimer's gene ALG-3

Emanuela Lacanà, J. Kelly Ganjei, Pasquale Vito, Luciano D'Adamio

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Recent attention has been focused on the members of the IL-1β-converting enzyme (ICE)/Ced-3 family of cysteine protease as the key components of programmed cell death. However, the molecular events that lead to protease activation and link it to the final apoptotic processes remain poorly characterized. We have shown recently that ALG-2 is a Ca2+-binding protein required for apoptosis. ALG-2 depletion protects the mouse T cell hybridoma 3DO from programmed cell death induced by several stimuli, such as synthetic glucocorticoids, TCR, and Fas triggering. In this work, we show that in the ALG-2-depleted clones the ICE/Ced-3 proteases are normally activated upon TCR, Fas, and dexamethasone stimulation, as determined by cleavage of the endogenous substrate poly(ADP-ribose) polymerase and of a fluorogenic substrate. ALC-3, a truncated form of the familial Alzheimer's disease gene PS2, confers resistance to TCR- and Fas-induced apoptosis. Of interest, it also reduces protease activity and inhibits poly(ADP-ribose) polymerase cleavage upon Fas triggering. Our results suggest that, during apoptosis, ALG-2 functions downstream of, and that ALC-3 interferes with the sequential activation of members of the ICE family proteases.

Original languageEnglish (US)
Pages (from-to)5129-5135
Number of pages7
JournalJournal of Immunology
Volume158
Issue number11
StatePublished - 1997
Externally publishedYes

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Interleukin-1
Peptide Hydrolases
Apoptosis
Poly(ADP-ribose) Polymerases
Enzymes
Genes
Cell Death
Cysteine Proteases
Hybridomas
Fluorescent Dyes
Dexamethasone
Glucocorticoids
Carrier Proteins
Alzheimer Disease
Clone Cells
T-Lymphocytes

ASJC Scopus subject areas

  • Immunology

Cite this

Dissociation of apoptosis and activation of IL-1β-converting enzyme/ced-3 proteases by ALG-2 and the truncated Alzheimer's gene ALG-3. / Lacanà, Emanuela; Ganjei, J. Kelly; Vito, Pasquale; D'Adamio, Luciano.

In: Journal of Immunology, Vol. 158, No. 11, 1997, p. 5129-5135.

Research output: Contribution to journalArticle

Lacanà, Emanuela ; Ganjei, J. Kelly ; Vito, Pasquale ; D'Adamio, Luciano. / Dissociation of apoptosis and activation of IL-1β-converting enzyme/ced-3 proteases by ALG-2 and the truncated Alzheimer's gene ALG-3. In: Journal of Immunology. 1997 ; Vol. 158, No. 11. pp. 5129-5135.
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