Open AccessProtein kinase Cμ downregulation of tumor‐necrosis‐factor‐induced apoptosis correlates with enhanced expression of nuclear‐factor‐κB‐dependent protective genes
Author(s) -
Johannes FranzJosef,
Horn Judith,
Link Gisela,
Haas Elvira,
Siemienski Katrin,
Wajant Harald,
Pfizenmaier Klaus
Publication year - 1998
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1998.2570047.x
Subject(s) - transactivation , biology , microbiology and biotechnology , signal transduction , downregulation and upregulation , death domain , tumor necrosis factor alpha , transcription factor , apoptosis , gene , programmed cell death , biochemistry , endocrinology
Protein kinase Cμ (PKCμ) represents a new subtype of the PKC family characterized by the presence of a pleckstrin homology (PH) domain and an amino‐terminal hydrophobic region. In order to analyse the potential role of PKCμ in signal‐transduction pathways, stable PKCμ transfectants were established with human and murine cell lines. All transfectants showed a reduced sensitivity to tumor‐necrosis‐factor (TNF)‐induced apoptosis, which correlated with the amount of transgene expressed and with an enhanced basal transcription rate of NF‐κB‐driven genes including the inhibitor of apoptosis protein 2 (cIAP2) and TNF‐receptor‐associated protein 1 (TRAF1). Sensitivity to apoptosis induced by the lipid mediator ceramide was unchanged in PKCμ transfectants. In support of a PKCμ action on NF‐κB, we show enhancement and downregulation of TNF‐induced expression of a NF‐κB‐dependent reporter gene by transient overexpression of wild‐type and kinase‐negative mutants of PKCμ, respectively. Interestingly, no significant changes were found in an electrophoretic mobility shift assay, indicative of PKCμ action downstream of IκB degradation, probably by modulation of the transactivation capacity of NF‐κB. The dominant negative action of the kinase‐negative mutant further suggest a regulatory role of PKCμ for NF‐κB‐dependent gene expression.