Related Experiment Video

Updated: Jan 6, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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MK5 Regulates YAP Stability and Is a Molecular Target in YAP-Driven Cancers

Jimyung Seo1, Min Hwan Kim1,2, Hyowon Hong1

  • 1Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, Korea.

Cancer Research
|October 4, 2019
PubMed

Insights

The serine/threonine kinase MK5 stabilizes the YAP oncoprotein, promoting cancer growth. Targeting MK5 offers a new therapeutic strategy for YAP-driven cancers by disrupting YAP degradation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The transcriptional regulator YAP is frequently activated in human cancers, driving tumor initiation, progression, metastasis, and drug resistance.
  • Targeting the Hippo-YAP pathway is challenging due to its low druggability and incomplete understanding of YAP regulation in cancer.

Purpose of the Study:

  • To identify novel therapeutic targets for YAP-driven tumorigenesis.
  • To elucidate the regulatory mechanisms controlling YAP stability in cancer.

Main Methods:

  • Functional RNAi screening in an oncogenic YAP activation model.
  • Co-immunoprecipitation to assess protein interactions.
  • Analysis of YAP ubiquitination and degradation.
  • Assessment of cell survival and xenograft tumor growth.
  • Correlation analysis with clinical tumor samples.

Main Results:

  • The serine/threonine kinase MK5 was identified as a novel positive regulator of YAP.
  • MK5 physically interacts with YAP, protecting it from CK1δ/ε-mediated ubiquitination and degradation independently of LATS1/2.
  • MK5 kinase activity is crucial for maintaining YAP stability and cytoplasmic localization.
  • Downregulation of MK5 inhibited survival in YAP-activated cancer cells and xenograft models.
  • MK5 upregulation correlated with high YAP expression and poor prognosis in clinical samples.

Conclusions:

  • MK5 is a novel kinase that regulates YAP stability in a LATS-independent manner.
  • Targeting the MK5-YAP interaction or MK5 activity presents a potential therapeutic strategy for YAP-driven cancers.

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