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.

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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