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Updated: Mar 7, 2026

Analysis of the c-KIT Ligand Promoter Using Chromatin Immunoprecipitation
Published on: June 27, 2017
STAT3 and ERK pathways are involved in cell growth stimulation of the ST2/IL1RL1 promoter
Kenji Tago1, Satoshi Ohta1, Megumi Funakoshi-Tago2
1Division of Structural Biochemistry Jichi Medical University Shimotsuke Tochigi Japan.
Abstract:
The ST2 gene was originally identified as a primary responsive gene induced by stimulation with growth factors and by oncogenic stress. The ST2 gene harbors two distinct promoters - a distal promoter and a proximal promoter. In this study, we identified a novel type of serum-responsive element in the ST2 proximal promoter using reporter gene analysis; this element includes a possible responsive element for STAT family proteins. Indeed, enforced expression of constitutively active STAT3 activated this promoter element and induced the expression of ST2 gene products. Furthermore, an oncogenic Ras (G12V) mutant also caused the expression of ST2 gene products by utilizing the proximal promoter. We also clarified that activation of the ST2 promoter by either growth stimulation or oncogenic Ras was suppressed by the inhibitors for STAT3 and ERK pathways. Our observations strongly suggest the importance of STAT family and ERK pathways for the induction of ST2 gene products by cell growth stimulation.
Insights
The ST2 gene
Area of Science:
- Molecular Biology
- Gene Regulation
- Oncology
Background:
- The ST2 gene is induced by growth factors and oncogenic stress.
- ST2 possesses distinct distal and proximal promoters.
Purpose of the Study:
- To identify novel regulatory elements in the ST2 proximal promoter.
- To elucidate the role of STAT and ERK pathways in ST2 gene induction.
Main Methods:
- Reporter gene analysis to identify serum-responsive elements.
- Enforced expression of constitutively active STAT3 and oncogenic Ras (G12V).
- Utilized pathway inhibitors (STAT3 and ERK).
Main Results:
- A novel serum-responsive element in the ST2 proximal promoter was identified.
- STAT3 activation and oncogenic Ras (G12V) induced ST2 gene expression via the proximal promoter.
- STAT3 and ERK pathway inhibitors suppressed ST2 promoter activation.
Conclusions:
- STAT family and ERK pathways are crucial for ST2 gene induction by growth stimulation and oncogenic Ras.
- The ST2 proximal promoter plays a key role in mediating responses to growth factors and oncogenic stress.
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