%0 Journal Article
%T PKC-¦Ä mediates interferon-¦Á-induced apoptosis through c-Jun NH2-terminal kinase activation
%A Noriko Yanase
%A Miho Hayashida
%A Yuki Kanetaka-Naka
%A Akinori Hoshika
%A Junichiro Mizuguchi
%J BMC Cell Biology
%D 2012
%I BioMed Central
%R 10.1186/1471-2121-13-7
%X IFN-¦Á caused activation of PKC-¦Ä in Daudi B lymphoma cells and myeloma U266 cells, as detected by Western blotting using a monoclonal antibody specific for the phosphorylated form of PKC-¦Ä. The dominant-negative form of mutant PKC-¦Ä (dnPKC-¦Ä) reduced the IFN-¦Á-induced JNK1 activation, TRAIL promoter activity, loss of mitochondrial membrane potential (¦¤¦·m), and increase in propidium iodide (PI) positive cells. The IFN-¦Á-induced activation of JNK1 and the TRAIL promoter was also attenuated by the PKC-¦Ä inhibitor rottlerin. Moreover, a constitutively active form of mutant PKC-¦Ä enhanced the IFN-¦Á-induced TRAIL promoter activity and loss of ¦¤¦·m in Daudi B lymphoma cells. In addition, IFN-¦Á-induced Ser727 phosphorylation of Stat1 was also abrogated by dnPKC-¦Ä.IFN-¦Á induced JNK1 activation via PKC-¦Ä, leading to upregulation of TRAIL. The interaction of the consequent enhanced TRAIL expression with TRAIL-receptor results in a loss of ¦¤¦·m and increase in PI positive cells. The IFN-¦Á-induced apoptotic events may also be affected by the Ser727-Stat1 induced by PKC-¦Ä-mediated signaling component(s).Type I interferon-¦Á (IFN-¦Á) has been employed for treatment of patients with some tumors including hairy cell leukemia, chronic myelogenous leukemia, melanoma, and renal cell cancer [1,2]. The anti-tumor action of IFN-¦Á is mediated at least by induction of apoptosis or inhibition of cell growth [3-6]. However, the detailed molecular mechanism(s) by which IFN-¦Á induces apoptosis remain largely unclear. The interaction of IFN-¦Á with its receptor results in transphosphorylation of receptor-associated Janus kinases (Jak1 and Tyk2), leading to tyrosine phosphorylation of critical residues on the receptors [7,8]. The activated Jak1/Tyk2 phosphorylate and activate signal transducers and activators of transcription (STAT), which in turn translocates to the nucleus to regulate gene transcription [8].In addition to Jak/Stat pathways, mitogen-activated protein kinases (MAPKs) including extrace
%K Interferon-¦Á
%K PKC-¦Ä
%K JNKs
%K Apoptosis
%K B lymphoma cells
%U http://www.biomedcentral.com/1471-2121/13/7