Complementation of a mutant cell line: central role of the 91 kDa polypeptide of ISGF3 in the interferon‐alpha and ‐gamma signal transduction pathways.
Open accessAbstract
Mutants in complementation group U3, completely defective in the response of all genes tested to interferons (IFNs) alpha and gamma, do not express the 91 and 84 kDa polypeptide components of interferon-stimulated gene factor 3 (ISGF3), a transcription factor known to play a primary role in the IFN-alpha response pathway. The 91 and 84 kDa polypeptides are products of a single gene. They result from differential splicing and differ only in a 38 amino acid extension at the C-terminus of the 91 kDa polypeptide. Complementation of U3 mutants with cDNA constructs expressing the 91 kDa product at levels comparable to those observed in induced wild-type cells completely restored the response to both IFN-alpha and -gamma and the ability to form ISGF3. Complementation with the 84 kDa component similarly restored the ability to form ISGF3 and, albeit to a lower level, the IFN-alpha response of all genes tested so far. It failed, however, to restore the IFN-gamma response of any gene analysed. The precise nature of the DNA motifs and combination of factors required for the transcriptional response of all genes inducible by IFN-alpha and -gamma remains to be established. The results presented here, however, emphasize the apparent general requirement of the 91 kDa polypeptide in the primary transcriptional response to both types of IFN.
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The cell line U3A does not express Stat1.
“the cell line U3A (data not shown), which does not express Stat1 (Müller et al. 1993).”
From DNA binding controls inactivation and nuclear accumulation of the transcription factor Stat1 (2003) · cites this paper as Müller et al. 1993
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Research works printed but not linked: 12
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- Authors
- Müller, M., Laxton, C., Briscoe, J., Schindler, C., Improta, T., Darnell, J. E., Stark, G. R., & Kerr, I. M.
- Venue
- The EMBO Journal
- Published
- 1993-11-01
- Volume
- 12
- Issue
- 11
- Pages
- 4221-4228
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC413716
- OpenAlex
- W318497777
- Cited by
- 411
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 4 · 2018: 5 · 2016: 8 · 2015: 2 · 2014: 9 · 2013: 10 · 2012: 6
- FWCI
- 14.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Molecular Biology Organization
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- ISGF3, interferon-alpha, interferon-gamma, interferon-stimulated genes, differential splicing, transcriptional response, mutant cell lines
- MeSH terms
- Base Sequence, Cell Line, DNA-Binding Proteins, Fibroblasts, Genetic Complementation Test, Humans, Interferon-gamma, Interferons, Molecular Sequence Data, Mutation, Protein Conformation, RNA, Messenger, Transcription Factors, Transcription, Genetic, Transfection, Signal Transduction, Interferon-alpha, Interferon-Stimulated Gene Factor 3, Interferon-Stimulated Gene Factor 3, gamma Subunit
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