IFNalpha/beta promotes cell survival by activating NF-kappa B.
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 IFNalpha/beta activates another important transcription factor, NF-kappaB. DNA-binding activity of NF-kappaB 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-kappaB activation in murine cells that express the human IFNalpha/beta receptor-1 signal-transducing chain of the type 1 IFN receptor. IFN promotes inhibitor of kappa B alpha (IkappaBalpha) serine phosphorylation and degradation, and stimulates NF-kappaB 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 IkappaBalpha, besides inhibiting IFN-mediated NF-kappaB activation and IkappaBalpha degradation, also enhanced apoptotic cell death in IFN-treated cells. We conclude that NF-kappaB activation by IFNalpha/beta is integrated into a signaling pathway through the IFNalpha/beta receptor-1 chain of the type 1 IFN receptor that promotes cell survival in apposition to various apoptotic stimuli.
Yang
C H
CH
Department of Pathology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Murti
A
A
Pfeffer
S R
SR
Basu
L
L
Kim
J G
JG
Pfeffer
L M
LM
D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D002470:Cell Survival / Q000502:physiology*; D015342:DNA Probes; D006868:Hydrolysis; D020672:I-kappa B Proteins / Q000737:chemistry / Q000378:metabolism; D016898:Interferon-alpha / Q000502:physiology*; D016899:Interferon-beta / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism
D015342:DNA Probes; D020672:I-kappa B Proteins; D016898:Interferon-alpha; D016328:NF-kappa B; D012694:Serine; D016899:Interferon-beta