Interferon alpha /beta promotes cell survival by activating nuclear factor kappa B through phosphatidylinositol 3-kinase and Akt

Interferons (IFNs) play critical roles in host defense by modulating gene expression via activation of signal transducer and activator of transcription (STAT) factors. IFN-alpha/beta also activates another transcription factor, nuclear factor kappaB (NF-kappaB), which protects cells against apoptoti...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-04, Vol.276 (17), p.13756-13761
Main Authors: Yang, C H, Murti, A, Pfeffer, S R, Kim, J G, Donner, D B, Pfeffer, L M
Format: Article
Language:English
Subjects:
a-Interferon
Akt protein
Apoptosis
b-Interferon
Cell Death
Cell Nucleus - metabolism
Cell Survival
Chromones - pharmacology
DNA-Binding Proteins - metabolism
Enzyme Inhibitors - pharmacology
Genes, Dominant
Humans
Interferon-alpha - physiology
Interferon-beta - physiology
Morpholines - pharmacology
NF-B protein
NF-kappa B - metabolism
Phosphatidylinositol 3-Kinases - metabolism
Protein-Serine-Threonine Kinases - metabolism
Proto-Oncogene Proteins - metabolism
Proto-Oncogene Proteins c-akt
Recombinant Proteins - metabolism
Signal Transduction
Stat3 protein
STAT3 Transcription Factor
Time Factors
Trans-Activators - metabolism
Transfection
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Summary:Interferons (IFNs) play critical roles in host defense by modulating gene expression via activation of signal transducer and activator of transcription (STAT) factors. IFN-alpha/beta also activates another transcription factor, nuclear factor kappaB (NF-kappaB), which protects cells against apoptotic stimuli. NF-kappaB activation requires the IFN-dependent association of STAT3 with the IFNAR1 chain of the IFN receptor. IFN-dependent NF-kappaB activation involves the sequential activation of a serine kinase cascade involving phosphatidylinositol 3-kinase (PI-3K) and Akt. Whereas constitutively active PI-3K and Akt induce NF-kappaB activation, Ly294002 (a PI-3K inhibitor), dominant-negative PI-3K, and kinase-dead Akt block IFN-dependent NF-kappaB activation. Moreover, dominant-negative PI-3K blocks IFN-promoted degradation of kappaBox alpha. Ly294002, a dominant-negative PI-3K construct, and kinase-dead Akt block IFN-promoted cell survival, enhancing apoptotic cell death. Therefore, STAT3, PI-3K, and Akt are components of an IFN signaling pathway that promotes cell survival through NF-kappaB activation.
ISSN:0021-9258
DOI:10.1074/jbc.M011006200