RGD Reference Report - Jun kinase delays caspase-9 activation by interaction with the apoptosome. - Rat Genome Database

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

Authors: Tran, TH  Andreka, P  Rodrigues, CO  Webster, KA  Bishopric, NH 
Citation: Tran TH, etal., J Biol Chem. 2007 Jul 13;282(28):20340-50. Epub 2007 May 4.
RGD ID: 2325744
Pubmed: PMID:17483091   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M702210200   (Journal Full-text)

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 H(2)O(2), JNK formed a stable association with oligomeric Apaf-1 in a approximately 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.



Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Apaf1Ratapoptosome  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Apaf1Ratidentical protein binding  IPIApaf1 (Rattus norvegicus)homooligomerizationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Apaf1  (apoptotic peptidase activating factor 1)


Additional Information