Nuclear translocation of STAT3 and NF-κB are independent of each other but NF-κB supports expression and activation of STAT3

Martincuks, Antons; Andryka, Katarzyna; Küster, Andrea; Schmitz-Van de Leur, Hildegard; Komorowski, Michal; Müller-Newen, Gerhard

doi:10.1016/j.cellsig.2017.01.006

Cited by 45NF-κB Signaling PathwaysCytokine Signaling Pathways and InteractionsSignaling Pathways in Disease

Nuclear translocation of STAT3 and NF-κB are independent of each other but NF-κB supports expression and activation of STAT3

Martincuks, Antons, Andryka, Katarzyna, Küster, Andrea, Schmitz-Van de Leur, Hildegard, Komorowski, Michal, Müller-Newen, Gerhard·2017·Cellular Signalling

DOI 10.1016/j.cellsig.2017.01.006

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Abstract

NF-κB and STAT3 are essential transcription factors in immunity and act at the interface of the transition from chronic inflammation to cancer. Different functional crosstalks between NF-κB and STAT3 have been recently described arguing for a direct interaction of both proteins. During a systematic analysis of NF-κB/STAT3 crosstalk we observed that appearance of the subcellular distribution of NF-κB and STAT3 in immunofluorescence heavily depends on the fixation procedure. Therefore, we established an optimized fixation protocol for the reliable simultaneous analysis of the subcellular distributions of both transcription factors. Using this protocol we found that cytokine-induced nuclear accumulation of NF-κB or STAT3 did not alter the subcellular distribution of the other transcription factor. Both knockout and overexpression of STAT3 does not have any major effect on canonical TNFα-NF-κB signalling in MEF or HeLa cells. Similarly, knockout of p65 did not alter nuclear accumulation of STAT3 in response to IL-6. However, p65 expression correlates with elevated total cellular levels of STAT3 and STAT1 and supports activation of these transcription factors. Our findings in MEF cells argue against a direct physical interaction of free cellular NF-κB and STAT3 but point to more intricate functional interactions.

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The suggested mechanisms for the STAT3-NF-κB crosstalk are often contradictory and a consensus has not been reached.
“Thus, the suggested mechanisms for the STAT3-NF-κB crosstalk are often contradictory and a consensus has not been reached.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [21]
Some studies suggest cooperation between STAT3 and NF-κB, while others show antagonism.
“Some suggest cooperation between them, while others show antagonism2, 16–21.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [21]
The crosstalk between STAT3 and NF-κB is an active field of research with studies showing contradictory outcomes of concomitant activation of the two TFs.
“The crosstalk between STAT3 and NF-κB is an active field of research with studies showing contradictory outcomes of concomitant activation of the two TFs.”
From Synergistic gene expression during the acute phase response is characterized by transcription factor assisted loading (2017) · cites this paper as [21]

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Authors: Martincuks, A., Andryka, K., Küster, A., Schmitz-Van de Leur, H., Komorowski, M., & Müller-Newen, G.
Affiliations: RWTH Aachen University (DE)
Institute of Fundamental Technological Research (PL)
ORCID: Martincuks, Antons
Andryka, Katarzyna
Müller-Newen, Gerhard
Venue: Cellular Signalling
Publisher: Elsevier BV
Published: 2017-04
Volume: 32
Pages: 36-47
ISSN: 0898-6568 (ISSN-L)
DOI: 10.1016/j.cellsig.2017.01.006
OpenAlex: W2570349166
Cited by: 45
References: 68
Citations by year: 2026: 7 · 2025: 5 · 2024: 6 · 2023: 1 · 2022: 2 · 2021: 8 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 1
FWCI: 1.47
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Cellular Signalling (publishedVersion)
PubMed (publishedVersion)
RWTH Publications (RWTH Aachen) (submittedVersion)
Funders: Studienstiftung des deutschen Volkes (AM, IZKF)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
Keywords: STAT3, NF-κB, nuclear translocation, transcription factor crosstalk, subcellular localization, interleukin-6, NF-κB p65, STAT1, chronic inflammation and cancer
MeSH terms: Animals, Cell Nucleus, Gene Expression Regulation, HeLa Cells, Humans, Tumor Necrosis Factor-alpha, NF-kappa B, Protein Transport, STAT1 Transcription Factor, STAT3 Transcription Factor, STAT5 Transcription Factor, Mice, Transcription Factor RelA

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Nuclear translocation of STAT3 and NF-κB are independent of each other but NF-κB supports expression and activation of STAT3

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