Jun kinase delays caspase-9 activation by interaction with the apoptosome

Thanh H. Tran, P. Andréka, Claudia O. Rodrigues, Keith A. Webster, Nanette H. Bishopric

Research output: Article

31 Citations (Scopus)

Abstract

Activation of c-Jun N-terminal kinase 1/2 (JNK) can delay oxidant-induced cell death, but the mechanism is unknown. We found that oxidant stress of cardiac myocytes activated both JNK and mitochondria-dependent apoptosis and that expression of JNK inhibitory mutants accelerated multiple steps in this pathway, including the cleavage and activation of caspases-3 and -9 and DNA internucleosomal cleavage, without affecting the rate of cytochrome c release; JNK inhibition also increased caspase-3 and -9 cleavage in a cell-free system. On activation by GSNO or H2O2, JNK formed a stable association with oligomeric Apaf-1 in a ∼1.4-2.0 mDa pre-apoptosome complex. Formation of this complex could be triggered by addition of cytochrome c and ATP to the cell-free cytosol. JNK inhibition abrogated JNK-Apaf-1 association and accelerated the association of procaspase-9 and Apaf-1 in both intact cells and cell-free extracts. We conclude that oxidant-activated JNK associates with Apaf-1 and cytochrome c in a catalytically inactive complex. We propose that this interaction delays formation of the active apoptosome, promoting cell survival during short bursts of oxidative stress.

Original languageEnglish
Pages (from-to)20340-20350
Number of pages11
JournalJournal of Biological Chemistry
Volume282
Issue number28
DOIs
Publication statusPublished - júl. 13 2007

Fingerprint

Apoptosomes
Mitogen-Activated Protein Kinase 9
Mitogen-Activated Protein Kinase 8
Caspase 9
Phosphotransferases
Chemical activation
Oxidants
Association reactions
Cytochromes c
Caspase 3
Cytochromes c1
DNA Cleavage
Mitochondria
Oxidative stress
Cell-Free System
Cell death
Cell Extracts
Cardiac Myocytes
Cytosol
Cell Survival

ASJC Scopus subject areas

  • Biochemistry

Cite this

Jun kinase delays caspase-9 activation by interaction with the apoptosome. / Tran, Thanh H.; Andréka, P.; Rodrigues, Claudia O.; Webster, Keith A.; Bishopric, Nanette H.

In: Journal of Biological Chemistry, Vol. 282, No. 28, 13.07.2007, p. 20340-20350.

Research output: Article

Tran, Thanh H. ; Andréka, P. ; Rodrigues, Claudia O. ; Webster, Keith A. ; Bishopric, Nanette H. / Jun kinase delays caspase-9 activation by interaction with the apoptosome. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 28. pp. 20340-20350.
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