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PMID: 8670109 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK) inhibits apoptosis by blocking the processing of CPP32.

The Biochemical journal ·Vol. 315 ( Pt 1) ·1996-04-01 ·Pages 21-4

Slee EA, Zhu H, Chow SC, MacFarlane M, Nicholson DW, Cohen GM

Abstract

Interleukin-1 beta converting enzyme (ICE)-like proteases, which are synthesized as inactive precursors, play a key role in the induction of apoptosis. We now demonstrate that benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD.FMK), an ICE-like protease inhibitor, inhibits apoptosis by preventing the processing of CPP32 to its active form. These results suggest that novel inhibitors of apoptosis can be developed which prevent processing of proforms of ICE-like proteases.

MeSH Terms
Amino Acid Chloromethyl Ketones/pharmacology Amino Acid Sequence Apoptosis/drug effects Caspase 3 Caspases Cysteine Endopeptidases/drug effects,metabolism Cysteine Proteinase Inhibitors/pharmacology Enzyme Activation/drug effects Humans Leukemia, Monocytic, Acute/enzymology,pathology Leukemia, T-Cell/enzymology,pathology Molecular Sequence Data Oligopeptides/pharmacology Poly(ADP-ribose) Polymerase Inhibitors Poly(ADP-ribose) Polymerases/metabolism Protease Inhibitors/pharmacology Tumor Cells, Cultured
Chemicals
Amino Acid Chloromethyl Ketones Cysteine Proteinase Inhibitors Oligopeptides Poly(ADP-ribose) Polymerase Inhibitors Protease Inhibitors acetyl-aspartyl-glutamyl-valyl-aspartal benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone Poly(ADP-ribose) Polymerases CASP3 protein, human Caspase 3 Caspases Cysteine Endopeptidases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Slee E A
MRC Toxicology Unit, University of Leicester, Lancaster Road, Leicester, U.K.
Zhu H
Chow S C
MacFarlane M
Nicholson D W
Cohen G M
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31 references, click to expand
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Article Info
Journal
The Biochemical journal
Abbr.
Biochem J
ISSN
0264-6021
DOI
10.1042/bj3150021
Published
1996-04-01
Pages
21-4
Language
English
Region
England
NLM ID
2984726R
PMCID
PMC1217173
Subset
IM
External Links
PubMed source DOI: 10.1042/bj3150021 PMC Full Text View journal details
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