Open AccessInduction of a Unique Isoform of theNCOA7Oxidation Resistance Gene by Interferon β-1b
Author(s) -
YuLijian,
CrozeEd,
D YamaguchiKen,
TranTiffany,
T RederAnthony,
LitvakVladimir,
Michael R. Volkert
Publication year - 2015
Publication title -
journal of interferon and cytokine research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.031
H-Index - 94
eISSN - 1557-7465
pISSN - 1079-9907
DOI - 10.1089/jir.2014.0115
Subject(s) - exon , janus kinase , biology , stat protein , gene isoform , janus kinase 2 , interferon , coactivator , alternative splicing , microbiology and biotechnology , gene , signal transduction , cancer research , transcription factor , genetics , stat3
We demonstrate that interferon (IFN)-β-1b induces an alternative-start transcript containing the C-terminal TLDc domain of nuclear receptor coactivator protein 7 (NCOA7), a member of the OXR family of oxidation resistance proteins. IFN-β-1b induces NCOA7-AS (alternative start) expression in peripheral blood mononuclear cells (PBMCs) obtained from healthy individuals and multiple sclerosis patients and human fetal brain cells, astrocytoma, neuroblastoma, and fibrosarcoma cells. NCOA7-AS is a previously undocumented IFN-β-inducible gene that contains only the last 5 exons of full-length NCOA7 plus a unique first exon (exon 10a) that is not found in longer forms of NCOA7. This exon encodes a domain closely related to an important class of bacterial aldo-keto oxido-reductase proteins that play a critical role in regulating redox activity. We demonstrate that NCOA7-AS is induced by IFN and LPS, but not by oxidative stress and exhibits, independently, oxidation resistance activity. We further demonstrate that induction of NCOA7-AS by IFN is dependent on IFN-receptor activation, the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, and a canonical IFN-stimulated response element regulatory sequence upstream of exon 10a. We describe a new role for IFN-βs involving a mechanism of action that leads to an increase in resistance to inflammation-mediated oxidative stress.