Non-conventional signal transduction by type 1 interferons: the NF-kappaB pathway.
Type I interferons (IFNs) regulate diverse cellular functions by modulating the expression of IFN-stimulated genes (ISGs) through the activation of the well established signal transduction pathway of the Janus Kinase (JAK) and signal transducers and activators of transcription (STAT) proteins. Although the JAK-STAT signal transduction pathway is critical in mediating IFN's antiviral and antiproliferative activities, other signaling pathways are activated by IFNs and regulate cellular response to IFN. The NF-kappaB transcription factor regulates the expression of genes involved in cell survival and immune responses. We have identified a novel IFN mediated signal pathway that leads to NF-kappaB activation and demonstrate that a subset of ISGs that play key roles in cellular response to IFN is regulated by NF-kappaB. This review focuses on the IFN-induced NF-kappaB activation pathway and the role of NF-kappaB in ISG expression, antiviral activity and apoptosis, and the therapeutic application of IFN in cancer and infectious disease.
Du
Ziyun
Z
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, University of Tennessee Cancer Institute, Memphis, Tennessee 38163, USA.
Wei
Lai
L
Murti
Aruna
A
Pfeffer
Susan R
SR
Fan
Meiyun
M
Yang
Chuan He
CH
Pfeffer
Lawrence M
LM
D000818:Animals; D005544:Forecasting; D015870:Gene Expression; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D053612:Janus Kinases / Q000502:physiology; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000502:physiology; D015398:Signal Transduction
D007370:Interferon Type I; D016328:NF-kappa B; D050791:STAT Transcription Factors; D053612:Janus Kinases