Open AccessIFNα/β promotes cell survival by activating NF-κB
Author(s) -
Chuan Yang,
Aruna Murti,
Susan R. Pfeffer,
Leela Basu,
Jong G. Kim,
Lawrence M. Pfeffer
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.250477397
Subject(s) - signal transduction , biology , microbiology and biotechnology , stat protein , transcription factor , phosphorylation , receptor , nfkb1 , apoptosis , programmed cell death , stat3 , gene , biochemistry
IFNs play critical roles in host defense by modulating the expression of various genes via signal transducer and activator of transcription factors. We show that IFNα/β activates another important transcription factor, NF-κB. DNA-binding activity of NF-κB was induced by multiple type 1 IFNs and was promoted by IFN in a diverse group of human, monkey, rat, and murine cells. Human IFN promoted NF-κB activation in murine cells that express the human IFNα/β receptor-1 signal-transducing chain of the type 1 IFN receptor. IFN promotes inhibitor of kappa B α (IκBα) serine phosphorylation and degradation, and stimulates NF-κB DNA-binding and transcriptional activity. Importantly, IFN promotes cell survival by protecting cells against a variety of proapoptotic stimuli, such as virus infection and antibody-mediated crosslinking. Expression of superrepressor forms of IκBα, besides inhibiting IFN-mediated NF-κB activation and IκBα degradation, also enhanced apoptotic cell death in IFN-treated cells. We conclude that NF-κB activation by IFNα/β is integrated into a signaling pathway through the IFNα/β receptor-1 chain of the type 1 IFN receptor that promotes cell survival in apposition to various apoptotic stimuli.