Characterization of beta-R1, a gene that is selectively induced by interferon beta (IFN-beta) compared with IFN-alpha.
We report preliminary characterization of a gene designated beta-R1, which is selectively expressed in response to interferon beta (IFN-beta) compared with IFN-alpha. In human astrocytoma cells, beta-R1 was induced to an equivalent extent by 10 IU/mL IFN-beta or 2500 IU/mL IFN-alpha2. To address the mechanism of this differential response, we analyzed induction of the beta-R1 gene in fibrosarcoma cells and derivative mutant cells lacking components required for signaling by type I IFNs. beta-R1 was readily induced by IFN-beta in the parental 2fTGH cell line, but not by recombinant IFN-alpha2, IFN-alpha Con1, or a mixture of IFN-alpha subtypes. IFN-alpha8 induced beta-R1 weakly. beta-R1 was not induced by IFN-beta in mutant cell lines U2A, U3A, U4A, and U6A, which lack, respectively, p48, STAT1, JAK1, and STAT2. U5A cells, which lack the Ifnar 2.2 component of the IFN-alpha and -beta receptor, also failed to express beta-R1. U1A cells are partially responsive to IFN-beta and IFN-alpha8 but lacked beta-R1 expression, indicating that TYK2 protein is essential for induction of this gene. Taken together, these results suggest that the expression of beta-R1 in response to type I IFN requires IFN-stimulated gene factor 3 plus an additional component, which is more efficiently formed on induction by IFN-beta compared with IFN-alpha.
Rani
M R
MR
Department of Neurosciences, Research Institute, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Foster
G R
GR
Leung
S
S
Leaman
D
D
Stark
G R
GR
Ransohoff
R M
RM
D001254:Astrocytoma / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D005354:Fibrosarcoma / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D008565:Membrane Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000235:genetics*; D050794:STAT1 Transcription Factor; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C507964:IFNAR1 protein, human; D016898:Interferon-alpha; D008565:Membrane Proteins; D012333:RNA, Messenger; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D015534:Trans-Activators; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta; D007371:Interferon-gamma