DOI: 10.1084/jem.189.1.63. STAT3 Is Required for the gp130-mediated Full Activation of the c-<i>myc</i> Gene

STAT3 Is Required for the gp130-mediated Full Activation of the c-myc Gene

10.1084/jem.189.1.63

Crossref journal-article

Rockefeller University Press

The Journal of Experimental Medicine (291)

Abstract

The signal transducers and activators of transcription (STAT) family members have been implicated in regulating the growth, differentiation, and death of normal and transformed cells in response to either extracellular stimuli, including cytokines and growth factors, or intracellular tyrosine kinases. c-myc expression is coordinately regulated by multiple signals in these diverse cellular responses. We show that STAT3 mostly mediates the rapid activation of the c-myc gene upon stimulation of the interleukin (IL)-6 receptor or gp130, a signal transducing subunit of the receptor complexes for the IL-6 cytokine family. STAT3 does so most likely by binding to cis-regulatory region(s) of the c-myc gene. We show that STAT3 binds to a region overlapping with the E2F site in the c-myc promoter and this site is critical for the c-myc gene promoter– driven transcriptional activation by IL-6 or gp130 signals. This is the first identification of the linkage between a member of the STAT family and the c-myc gene activation, and also explains how the IL-6 family of cytokines is capable of inducing the expression of the c-myc gene.

Bibliography

Kiuchi, N., Nakajima, K., Ichiba, M., Fukada, T., Narimatsu, M., Mizuno, K., Hibi, M., & Hirano, T. (1999). STAT3 Is Required for the gp130-mediated Full Activation of the c-myc Gene. The Journal of Experimental Medicine, 189(1), 63â73.

Authors 8

Nobuo Kiuchi (first)
Koichi Nakajima (additional)
Makoto Ichiba (additional)
Toshiyuki Fukada (additional)
Masahiro Narimatsu (additional)
Katsunori Mizuno (additional)
Masahiko Hibi (additional)
Toshio Hirano (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:49 p.m.)
Deposited	2 years, 1 month ago (July 25, 2023, 5:48 a.m.)
Indexed	1 day, 2 hours ago (Aug. 28, 2025, 8:26 a.m.)
Issued	26 years, 7 months ago (Jan. 4, 1999)
Published	26 years, 7 months ago (Jan. 4, 1999)
Published Online	26 years, 7 months ago (Jan. 4, 1999)
Published Print	26 years, 7 months ago (Jan. 4, 1999)

Funders 0

None

BibTeX

@article{Kiuchi_1999, title={STAT3 Is Required for the gp130-mediated Full Activation of the c-myc Gene}, volume={189}, ISSN={1540-9538}, url={http://dx.doi.org/10.1084/jem.189.1.63}, DOI={10.1084/jem.189.1.63}, number={1}, journal={The Journal of Experimental Medicine}, publisher={Rockefeller University Press}, author={Kiuchi, Nobuo and Nakajima, Koichi and Ichiba, Makoto and Fukada, Toshiyuki and Narimatsu, Masahiro and Mizuno, Katsunori and Hibi, Masahiko and Hirano, Toshio}, year={1999}, month=jan, pages={63–73} }

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  "abstract": "<jats:p>The signal transducers and activators of transcription (STAT) family members have been implicated in regulating the growth, differentiation, and death of normal and transformed cells in response to either extracellular stimuli, including cytokines and growth factors, or intracellular tyrosine kinases. c-myc expression is coordinately regulated by multiple signals in these diverse cellular responses. We show that STAT3 mostly mediates the rapid activation of the c-myc gene upon stimulation of the interleukin (IL)-6 receptor or gp130, a signal transducing subunit of the receptor complexes for the IL-6 cytokine family. STAT3 does so most likely by binding to cis-regulatory region(s) of the c-myc gene. We show that STAT3 binds to a region overlapping with the E2F site in the c-myc promoter and this site is critical for the c-myc gene promoter\u2013 driven transcriptional activation by IL-6 or gp130 signals. This is the first identification of the linkage between a member of the STAT family and the c-myc gene activation, and also explains how the IL-6 family of cytokines is capable of inducing the expression of the c-myc gene.</jats:p>",
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