FLICE induced apoptosis in a cell-free system. Cleavage of caspase zymogens

Maria Muzio, Guy S. Salvesen, Vishva M. Dixit

Research output: Contribution to journalArticle

Abstract

Engagement of CD95 or tumor necrosis factor 1 receptor (TNFR-1) by ligand or agonist antibodies is capable of activating the cell death program, the effector arm of which is composed of mammalian interleukin-1β converting enzyme (ICE)-like cysteine proteases (designated caspases) that are related to the Caenorhabditis elegans death gene, CED-3. Caspases, unlike other mammalian cysteine proteases, cleave their substrates following aspartate residues. Furthermore, proteases belonging to this family exist as zymogens that in turn require cleavage at internal aspartate residues to generate the two-subunit active enzyme. As such, family members are capable of activating each other. Remarkably, both CD95 and TNFR-1 death receptors initiate apoptosis by recruiting a novel ICE/CED-3 family member, designated FLICE/MACH, to the receptor signaling complex. Therefore, FLICE/MACH represents the apical triggering protease in the cascade. Consistent with this, recombinant FLICE was found capable of proteolytically activating downstream caspases. Furthermore, CrmA, a pox virus-encoded serpin that inhibits Fas and tumor necrosis factor-induced cell death attenuates the ability of FLICE to activate downstream caspases.

Original languageEnglish
Pages (from-to)2952-2956
Number of pages5
JournalJournal of Biological Chemistry
Volume272
Issue number5
DOIs
Publication statusPublished - 1997

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Enzyme Precursors
Cell-Free System
Caspases
Apoptosis
Caspase 1
Cysteine Proteases
Tumor Necrosis Factor-alpha
Tumor Necrosis Factor Receptors
Cell death
Aspartic Acid
Peptide Hydrolases
Cell Death
Serpins
Death Domain Receptors
Aptitude
Caenorhabditis elegans
Viruses
Genes
Ligands
Antibodies

ASJC Scopus subject areas

  • Biochemistry

Cite this

FLICE induced apoptosis in a cell-free system. Cleavage of caspase zymogens. / Muzio, Maria; Salvesen, Guy S.; Dixit, Vishva M.

In: Journal of Biological Chemistry, Vol. 272, No. 5, 1997, p. 2952-2956.

Research output: Contribution to journalArticle

Muzio, Maria ; Salvesen, Guy S. ; Dixit, Vishva M. / FLICE induced apoptosis in a cell-free system. Cleavage of caspase zymogens. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 5. pp. 2952-2956.
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