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PMID: 11095741 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

IFNalpha/beta promotes cell survival by activating NF-kappa B.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 97 ·No. 25 ·2000-12-05 ·Pages 13631-6

Yang CH, Murti A, Pfeffer SR, Basu L, Kim JG, Pfeffer LM

Abstract

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.

MeSH Terms
Apoptosis/physiology Base Sequence Cell Survival/physiology DNA Probes Hydrolysis I-kappa B Proteins/chemistry,metabolism Interferon-alpha/physiology Interferon-beta/physiology NF-kappa B/metabolism Phosphorylation Serine/metabolism
Chemicals
DNA Probes I-kappa B Proteins Interferon-alpha NF-kappa B Serine Interferon-beta
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Yang C H
Department of Pathology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Murti A
Pfeffer S R
Basu L
Kim J G
Pfeffer L M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.250477397
Published
2000-12-05
Pages
13631-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC17627
Subset
IM
Grants
NCI NIH HHS · R01 CA073753 · United States
NCI NIH HHS · CA73753 · United States
External Links
PubMed source DOI: 10.1073/pnas.250477397 PMC Full Text View journal details
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