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Updated: Feb 28, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
The novel YAP target gene, SGK1, upregulates TAZ activity by blocking GSK3β-mediated TAZ destabilization
Geon Yoo1, Tackhoon Kim2, Chaeuk Chung3
1School of Biological Sciences, Seoul National University, Seoul 151-742, South Korea.
Abstract:
YAP (Yes-associated protein) and TAZ (transcription activator with PDZ binding motif) are important in tissue regeneration and cancer development, highlighting the importance of discovering partners that regulate their oncogenicity. SGK1 (serum/glucocorticoid regulated kinase 1), initially identified as a homolog of Akt in phosphoinositide 3-kinase signaling, acts as a serine/threonine protein kinase in multiple oncogenic pathways. However, possible links between SGK1 and Hippo-YAP/TAZ signaling remain unexplored. Here, we reveal that SGK1 is a potential positive feedback regulator of YAP and TAZ, showing that the TEAD-YAP/TAZ complex directly activates SGK1 transcription by binding to the distal enhancer of SGK1, and SGK1, in turn, stabilizes YAP/TAZ. Moreover, we demonstrate that expression of YAP/TAZ target genes is positively regulated by SGK1. Mechanistically, SGK1 inhibits ubiquitin-mediated degradation of TAZ by inhibiting GSK3β activity. These findings expand our understanding of YAP/TAZ regulation to include the novel downstream target of YAP, SGK1.
Insights
Serum/glucocorticoid regulated kinase 1 (SGK1) acts as a positive feedback regulator for Yes-associated protein (YAP) and transcription activator with PDZ binding motif (TAZ). SGK1 stabilizes YAP/TAZ, enhancing their oncogenic activity.
Area of Science:
- Cell Biology
- Molecular Oncology
- Signal Transduction
Background:
- Yes-associated protein (YAP) and transcription activator with PDZ binding motif (TAZ) are key regulators in tissue regeneration and cancer.
- Serum/glucocorticoid regulated kinase 1 (SGK1) is implicated in various oncogenic pathways.
- The interplay between SGK1 and the Hippo-YAP/TAZ signaling pathway is not well understood.
Purpose of the Study:
- To investigate the regulatory relationship between SGK1 and YAP/TAZ signaling.
- To elucidate the role of SGK1 in YAP/TAZ-mediated oncogenicity.
Main Methods:
- Analysis of SGK1 transcription activation by TEAD-YAP/TAZ complex.
- Assessment of SGK1's effect on YAP/TAZ protein stability.
- Investigation of SGK1's impact on YAP/TAZ target gene expression.
- Exploration of SGK1's mechanism in regulating TAZ degradation via GSK3β inhibition.
Main Results:
- The TEAD-YAP/TAZ complex directly upregulates SGK1 transcription.
- SGK1 enhances the stability of YAP and TAZ proteins.
- SGK1 positively regulates the expression of YAP/TAZ target genes.
- SGK1 inhibits the degradation of TAZ by suppressing GSK3β activity.
Conclusions:
- SGK1 acts as a positive feedback regulator of YAP/TAZ signaling.
- This interaction expands the understanding of YAP/TAZ regulation, identifying SGK1 as a novel downstream target.
- The findings highlight SGK1 as a potential therapeutic target in cancers driven by YAP/TAZ hyperactivity.
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