STAT3 orchestrates contradictory signals in cytokine-induced G1 to S cell-cycle transition
Open accessAbstract
The signal transducer and activator of transcription molecules (STATs) play key roles in cytokine-induced signal transduction. However, their role in cell growth has not been clear. In the present study, we show that STAT3 plays a key role in the G1 to S phase cell-cycle transition induced by the cytokine receptor subunit gp130, through the upregulation of cyclins D2, D3 and A, and cdc25A, and the concomitant downregulation of p21 and p27. Furthermore, unexpectedly, we found that gp130 could induce the expression of p21 when STAT3 activation was suppressed. Such contradictory signals regulating cell-cycle progression could be simultaneously delivered from distinct cytoplasmic regions of gp130. We propose an 'orchestrating model' for cytokine and growth factor action in which contradictory signals are orchestrated to produce a specific effect in a target cell.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Gp130-mediated activation of STAT3 is involved in cell-cycle transition through up-regulation of cyclins D2, D3 and A, and cdc25A, and concomitant down-regulation of p21 and p27, while p21 is induced when STAT3 activation is suppressed, indicating the balance of contradictory signals determines the final output.
“The gp130-mediated activation of STAT3 is involved in the cell-cycle transition through the up-regulation of cyclins D2, D3 and A, and cdc25A, and the concomitant down-regulation of p21 and p27, while p21 is induced when STAT3 activation is suppressed, indicating the balance of contradictory signals determines the final output (110).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [110]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Sherr, C. J. (1996) · Science · doi:10.1126/science.274.5293.1672 · Cited by 5,379 · see citing works
Lütticken, C., Wegenka, U. M., Yuan, J., Buschmann, J., Schindler, C., Ziemiecki, A., Harpur, A. G., Wilks, A. F., Yasukawa, K., Taga, T., et al. (1994) · Science · doi:10.1126/science.8272872 · Cited by 814 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Fujii,H. et al. (1995) Activation of STAT5 by interleukin 2 requires a carboxyltermianal region of interleukin 2 receptor β chain but is not essential for the proliferative signal transmission. Proc. Natl Acad. Sci. USA, 92, 5482-5486.
Cited by
Sorted by citations
IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
“STAT3 is involved not only in bcl-2 induction, but also in the induction of c-myc, cyclins and Pim1/2 kinase to regulate cell survival and cell cycle progression in a pre-B-cell line (110, 126, 127).”
BackgroundSelf-citationStat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis
Bowman, T., Broome, M. A., Sinibaldi, D., Wharton, W., Pledger, W. J., Sedivy, J. M., Irby, R., Yeatman, T., Courtneidge, S. A., & Jove, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.131568898 · Cited by 488 · see citing works
Interleukin 6 and liver regeneration
STREETZ, K. L., LUEDDE, T., MANNS, M. P., & TRAUTWEIN, C. (2000) · Gut · doi:10.1136/gut.47.2.309 · Cited by 238 · see citing works
Interleukin-6 signalling: More than Jaks and STATs
Eulenfeld, R., Dittrich, A., Khouri, C., Müller, P. J., Mütze, B., Wolf, A., & Schaper, F. (2012) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2011.09.010 · Cited by 171 · see citing works
Moodley, Y. P., Scaffidi, A. K., Misso, N. L., Keerthisingam, C., McAnulty, R. J., Laurent, G. J., Mutsaers, S. E., Thompson, P. J., & Knight, D. A. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63658-9 · Cited by 165 · see citing works
Expression of suppressors of cytokine signaling during liver regeneration
Campbell, J. S., Prichard, L., Schaper, F., Schmitz, J., Stephenson-Famy, A., Rosenfeld, M. E., Argast, G. M., Heinrich, P. C., & Fausto, N. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11867 · Cited by 156 · see citing works
Begue, G., Douillard, A., Galbes, O., Rossano, B., Vernus, B., Candau, R., & Py, G. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057141 · Cited by 124 · see citing works
Molecular basis of the cell specificity of cytokine action
Ishihara, K., & Hirano, T. (2002) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(02)00321-x · Cited by 122 · see citing works
Self-citation
- Authors
- Fukada, T., Ohtani, T., Yoshida, Y., Shirogane, T., Nishida, K., Nakajima, K., Hibi, M., & Hirano, T.
- Affiliations
- The University of Osaka (JP)
- Osaka City University (JP)
- Corresponding author
- Hirano, Toshio
- Venue
- The EMBO Journal
- Published
- 1998-11-16
- Volume
- 17
- Issue
- 22
- Pages
- 6670-6677
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1171012
- OpenAlex
- W1977370355
- Cited by
- 247
- References
- 2
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 5 · 2023: 12 · 2022: 9 · 2021: 5 · 2020: 4 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 3 · 2013: 11 · 2012: 11
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- STAT3, gp130, cytokine signaling, G1/S transition, cyclin D2, cyclin D3, cyclin A, CDC25A, p21, p27, cell cycle regulation
- MeSH terms
- Cell Line, DNA-Binding Proteins, Enzyme Activation, Enzyme Inhibitors, Signal Transduction, Trans-Activators, Down-Regulation, G1 Phase, S Phase, Cytokines, Cyclin-Dependent Kinases, STAT3 Transcription Factor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
