MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin-induced apoptosis

Détails

ID Serval
serval:BIB_075D6494BCED
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
MEK kinase 1, a substrate for DEVD-directed caspases, is involved in genotoxin-induced apoptosis
Périodique
Molecular and Cellular Biology
Auteur⸱e⸱s
Widmann  C., Gerwins  P., Johnson  N. L., Jarpe  M. B., Johnson  G. L.
ISSN
0270-7306 (Print)
Statut éditorial
Publié
Date de publication
04/1998
Volume
18
Numéro
4
Pages
2416-29
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Apr
Résumé
MEK kinase 1 (MEKK1) is a 196-kDa protein that, in response to genotoxic agents, was found to undergo phosphorylation-dependent activation. The expression of kinase-inactive MEKK1 inhibited genotoxin-induced apoptosis. Following activation by genotoxins, MEKK1 was cleaved in a caspase-dependent manner into an active 91-kDa kinase fragment. Expression of MEKK1 stimulated DEVD-directed caspase activity and induced apoptosis. MEKK1 is itself a substrate for CPP32 (caspase-3). A mutant MEKK1 that is resistant to caspase cleavage was impaired in its ability to induce apoptosis. These findings demonstrate that MEKK1 contributes to the apoptotic response to genotoxins. The regulation of MEKK1 by genotoxins involves its activation, which may be part of survival pathways, followed by its cleavage, which generates a proapoptotic kinase fragment able to activate caspases. MEKK1 and caspases are predicted to be part of an amplification loop to increase caspase activity during apoptosis.
Mots-clé
Animals *Apoptosis/drug effects Ca(2+)-Calmodulin Dependent Protein Kinase/metabolism Caspase 3 *Caspases Cell Line Cysteine Endopeptidases/*metabolism Cysteine Proteinase Inhibitors/pharmacology DNA Damage DNA Fragmentation Enzyme Activation Humans Inhibitor of Apoptosis Proteins JNK Mitogen-Activated Protein Kinases *MAP Kinase Kinase Kinase 1 Mice *Mitogen-Activated Protein Kinases Mutagens/*pharmacology Mutation Oligopeptides/metabolism Peptide Fragments/metabolism Phosphorylation Protein-Serine-Threonine Kinases/genetics/*metabolism/radiation effects Protein-Tyrosine Kinases/genetics/*metabolism/radiation effects Serpins/pharmacology Substrate Specificity Transfection Ultraviolet Rays Viral Proteins/pharmacology
Pubmed
Web of science
Création de la notice
24/01/2008 15:43
Dernière modification de la notice
20/08/2019 13:29
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