Apoptosis stimulated by the 91-kDa caspase cleavage MEKK1 fragment requires translocation to soluble cellular compartments.

Details

Serval ID
serval:BIB_5AB5FAF269BA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Apoptosis stimulated by the 91-kDa caspase cleavage MEKK1 fragment requires translocation to soluble cellular compartments.
Journal
Journal of Biological Chemistry
Author(s)
Schlesinger T.K., Bonvin C., Jarpe M.B., Fanger G.R., Cardinaux J.R., Johnson G.L., Widmann C.
ISSN
0021-9258
Publication state
Published
Issued date
03/2002
Peer-reviewed
Oui
Volume
277
Number
12
Pages
10283-10291
Language
english
Abstract
MEKK1, a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase, generates anti-apoptotic signaling as a full-length protein but induces apoptosis when cleaved by caspases. Here, we show that caspase-dependent cleavage of MEKK1 relocalizes the protease-generated 91-kDa kinase fragment from a particulate fraction to a soluble cytoplasmic fraction. Relocalization of MEKK1 catalytic activity is necessary for the pro-apoptotic function of MEKK1. The addition of a membrane-targeting signal to the 91-kDa fragment inhibits caspase activation and the induction of apoptosis but does not change the activation of JNK, ERK, NFkappaB, or p300. These results identify the caspase cleavage of MEKK1 as a dynamic regulatory mechanism that alters the subcellular distribution of MEKK1, changing its function to pro-apoptotic signaling, which does not depend on the currently described MEKK1 effectors.
Keywords
Animals, Apoptosis, Blotting, Western, Catalysis, Cell Line, Cell Membrane/enzymology, Cell Nucleus/enzymology, Cytoplasm/enzymology, Cytoplasm/metabolism, DNA, Complementary/metabolism, Dose-Response Relationship, Drug, E1A-Associated p300 Protein, Humans, MAP Kinase Kinase Kinase 1, Mice, Microscopy, Fluorescence, Mitogen-Activated Protein Kinase 8, Mitogen-Activated Protein Kinases/metabolism, NF-kappa B/metabolism, Nuclear Proteins/metabolism, Plasmids/metabolism, Protein Binding, Protein Structure, Tertiary, Protein Transport, Protein-Serine-Threonine Kinases/chemistry, Protein-Serine-Threonine Kinases/metabolism, Subcellular Fractions/metabolism, Time Factors, Trans-Activators/metabolism, Transfection, Ultraviolet Rays
Pubmed
Web of science
Open Access
Yes
Create date
18/02/2008 10:32
Last modification date
20/08/2019 14:13
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