Related Experiment Videos
STAT3 is required for the gp130-mediated full activation of the c-myc gene
N Kiuchi1, K Nakajima, M Ichiba
1Division of Molecular Oncology, Biomedical Research Center, Osaka University Medical School, Suita, Osaka 565-0871, Japan.
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.
Insights
Signal transducers and activators of transcription 3 (STAT3) directly activate the c-myc gene. This STAT3 binding to the c-myc promoter explains how interleukin-6 (IL-6) signaling induces c-myc expression.
Area of Science:
- Molecular Biology
- Cell Signaling
- Gene Regulation
Background:
- Signal transducers and activators of transcription (STAT) proteins regulate cell growth, differentiation, and death.
- c-myc gene expression is crucial in various cellular responses and is tightly controlled by multiple signaling pathways.
Purpose of the Study:
- To investigate the role of STAT family members in c-myc gene activation.
- To elucidate the mechanism by which interleukin-6 (IL-6) and related cytokines induce c-myc expression.
Main Methods:
- Investigated STAT3's role in c-myc gene activation.
- Analyzed STAT3 binding to the c-myc promoter region.
- Assessed the impact of IL-6 and gp130 signaling on c-myc promoter activity.
Main Results:
- STAT3 was identified as a key mediator of rapid c-myc gene activation upon stimulation of the IL-6 receptor or gp130.
- STAT3 binds to a specific region within the c-myc promoter, overlapping with the E2F site.
- This STAT3 binding site is critical for IL-6 or gp130-induced transcriptional activation of the c-myc gene.
Conclusions:
- This study establishes a direct link between STAT3 and c-myc gene activation.
- The findings explain how the IL-6 cytokine family effectively induces c-myc gene expression through STAT3-mediated promoter binding.