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Updated: Apr 12, 2026
A Rapid In Vivo Bioassay for Developmentally Active Enhancers
The increased Sprouty4 expression in response to serum is transcriptionally controlled by Specific protein 1
Angelina Doriguzzi1, Barbara Haigl1, Andrea Gsur1
1Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria.
Abstract:
Sprouty proteins control length and intensity of the intracellular signal transduction cascade activated by mitogens in the cellular environment. As part of a negative feedback loop, their expression is supposed to be elevated by the same factors. In this report, Sprouty4 expression in response to serum and the underlying regulatory mechanisms were investigated. We verified that Sprouty4 expression is activated by serum addition in all tested cells independent of their origin. Strict correlation between Sprouty4 protein levels and promoter activity indicates mainly transcriptional regulation of Sprouty4 serum-responsiveness. Induction of the mitogen-activated protein kinase pathway is required for Sprouty4 promoter activation in the presence of serum. Nonetheless, signal transduction via this pathway is not sufficient to fully induce the Sprouty4 promoter. Instead, deletion and mutation analysis identified two annotated Specific protein 1 binding sites as the critical cis-elements responsible for conferring the serum induction of the promoter. Corroborating, repressed Specific protein 1 activity or levels result in constitutive lowered transcriptional activity of the Sprouty4 promoter. These data demonstrate that Specific protein 1 plays a crucial role in the regulation of Sprouty4 in response to serum.
Insights
Sprouty4 expression increases with serum, primarily through transcriptional regulation. Specific protein 1 binding sites are critical for this serum-induced Sprouty4 promoter activation.
Area of Science:
- Cellular signaling and gene regulation.
- Molecular biology and signal transduction pathways.
Background:
- Sprouty proteins modulate mitogen-activated signaling cascades.
- Sprouty protein expression is typically upregulated by signaling activators as part of negative feedback.
Purpose of the Study:
- To investigate Sprouty4 expression regulation in response to serum.
- To identify the molecular mechanisms controlling Sprouty4 serum-responsiveness.
Main Methods:
- Analysis of Sprouty4 expression and promoter activity in response to serum.
- Mitogen-activated protein kinase pathway induction assays.
- Deletion and mutation analysis of the Sprouty4 promoter.
- Assessment of Specific protein 1 (Sp1) activity and its effect on promoter function.
Main Results:
- Sprouty4 expression is serum-inducible across various cell types.
- Transcriptional regulation is the primary mechanism for Sprouty4 serum-responsiveness.
- Mitogen-activated protein kinase pathway activation is necessary but insufficient for full Sprouty4 induction.
- Two Sp1 binding sites on the Sprouty4 promoter are essential for serum-induced activation.
- Reduced Sp1 activity leads to decreased Sprouty4 promoter activity.
Conclusions:
- Sprouty4 expression is transcriptionally controlled by serum.
- Specific protein 1 is a key transcription factor mediating Sprouty4 induction by serum.
- This identifies a critical regulatory role for Sp1 in Sprouty4 signaling.
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