Cited by 107Cytokine Signaling Pathways and InteractionsNF-κB Signaling PathwaysGenomics and Chromatin Dynamics

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Interleukin-4/STAT6 Represses STAT1 and NF-κB-dependent Transcription through Distinct Mechanisms

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Ohmori, Yoshihiro, Hamilton, Thomas A.·2000·Journal of Biological Chemistry

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Abstract

STAT6 mediates interleukin-4 (IL-4)-dependent positive and negative regulation of inflammatory gene expression. In the present report we examined the molecular mechanisms involved in IL-4-induced repression of reporter gene transcription driven by STAT1 and/or NF-kappaB. Transient expression of STAT6 in a STAT6-deficient cell line (HEK 293) conferred sensitivity to IL-4 for STAT6-dependent transcription and for repression of interferon-gamma (IFNgamma)/STAT1- and/or tumor necrosis factor-alpha (TNFalpha)/NF-kappaB-driven reporter gene expression. In cells transfected with a deletion mutant of STAT6 lacking its transactivating domain, IL-4 could not mediate either positive or negative control of reporter gene expression. Overexpression of CREB-binding protein dramatically enhanced IL-4/STAT6-stimulated transcription and overcame IL-4-mediated repression of TNFalpha/NF-kappaB-dependent but not IFNgamma/STAT1-dependent transcription. A single amino acid change in the DNA-binding domain of STAT6 (H415A) selectively reduced the affinity of STAT6 for IL-4-responsive STAT sequence motifs (N4) without affecting the affinity for IFNgamma-responsive (GAS) sequences (N3) and, accordingly, eliminated transcription from an IL-4-responsive promoter. Interestingly, this mutation eliminated IL-4-mediated suppression of reporter gene transcription stimulated by TNFalpha/NF-kappaB but retained nearly full capacity to suppress IFNgamma/STAT1-stimulated transcription. Taken together these results demonstrate that STAT6 mediates suppression of STAT1 and NF-kappaB-dependent transcription by distinct mechanisms. Both processes are dependent upon the STAT6 transactivation domain and may involve sequestration of necessary but different transcriptional coactivator proteins. These two suppressive mechanisms are controlled differentially by the nature of the STAT6 DNA-binding site (i.e. N3 versus N4).

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Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease
Chirgwin, J. M., Przybyla, A., MacDonald, R. J., & Rutter, W. J. (1979) · Biochemistry · doi:10.1021/bi00591a005 · Cited by 21,460
Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei
Dignam, J. D., Lebovitz, R. M., & Roeder, R. G. (1983) · Nucleic Acids Research · doi:10.1093/nar/11.5.1475 · Cited by 11,262
TH1 and TH2 Cells: Different Patterns of Lymphokine Secretion Lead to Different Functional Properties
Mosmann, T. R., & Coffman, R. L. (1989) · Annual Review of Immunology · doi:10.1146/annurev.iy.07.040189.001045 · Cited by 7,692
Jak-STAT Pathways and Transcriptional Activation in Response to IFNs and Other Extracellular Signaling Proteins
Darnell, J. E., Kerr, L. M., & Stark, G. R. (1994) · Science · doi:10.1126/science.8197455 · Cited by 6,080
Functional diversity of helper T lymphocytes
Abbas, A. K., MURPHY, K. M. M., & Sher, A. (1996) · Nature · doi:10.1038/383787a0 · Cited by 4,432
A CBP Integrator Complex Mediates Transcriptional Activation and AP-1 Inhibition by Nuclear Receptors
Kamei, Y., Xu, L., Heinzel, T., Torchia, J., Kurokawa, R., Gloss, B., Lin, S.-C., Heyman, R. A., Rose, D. W., Glass, C. K., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81118-6 · Cited by 2,150
Maximal activation of transcription by statl and stat3 requires both tyrosine and serine phosphorylation
Wen, Z., Zhong, Z., & Darnell, J. E. (1995) · Cell · doi:10.1016/0092-8674(95)90311-9 · Cited by 1,974
TRANSCRIPTIONAL RESPONSES TO POLYPEPTIDE LIGANDS: The JAK-STAT Pathway
Schindler, C., & Darnell, J. E. (1995) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.64.070195.003201 · Cited by 1,808
The IL-4 receptor: signaling mechanisms and biologic functions
Nelms, K., Keegan, A. D., Zamorano, J., Ryan, J. J., & Paul, W. E. (1999) · Annual Review of Immunology · doi:10.1146/annurev.immunol.17.1.701 · Cited by 1,545
Cytokines Induce the Development of Functionally Heterogeneous T Helper Cell Subsets
O’Garra, A. (1998) · Immunity · doi:10.1016/s1074-7613(00)80533-6 · Cited by 1,527

Show all 68 references

Research works printed but not linked: 3

Sims, 1993, Mol. Cell. Biol., 13, 690
Dokter, 1996, Leukemia (Baltimore ), 10, 1308
Luo, 2000, Mol. Endocrinol., 14, 114

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Authors: Ohmori, Y., & Hamilton, T. A.
Affiliations: Cleveland Clinic (US)
Corresponding author: Ohmori, Yoshihiro
ORCID: Ohmori, Yoshihiro
Hamilton, Thomas A.
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 2000-12
Volume: 275
Issue: 48
Pages: 38095-38103
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.m006227200
OpenAlex: W2015491183
Cited by: 106
References: 68
Citations by year: 2026: 3 · 2025: 3 · 2024: 2 · 2023: 4 · 2021: 4 · 2020: 5 · 2019: 1 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 2 · 2014: 6 · 2013: 5 · 2012: 3
FWCI: 3.83
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7244 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: National Cancer Institute (CA62220, P01CA062220)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: IL-4, STAT6, STAT1, NF-κB, transcriptional repression, interferon-gamma, TNF-α, CREB-binding protein, DNA-binding domain, transcriptional coactivator, inflammatory gene expression
MeSH terms: Base Sequence, Cell Line, DNA-Binding Proteins, Humans, Interferon-gamma, Phosphoproteins, Transcription, Genetic, Tumor Necrosis Factor-alpha, Trans-Activators, Interleukin-4, NF-kappa B, DNA Primers, STAT6 Transcription Factor, Interferon Regulatory Factor-1

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Interleukin-4/STAT6 Represses STAT1 and NF-κB-dependent Transcription through Distinct Mechanisms

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