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Updated: Jun 28, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
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SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors

Hui Qian1, Chen-Hong Ding2, Fang Liu1

  • 1Department of Gastroenterology, Changzheng Hospital, Naval Medical University, Shanghai, China.

Signal Transduction and Targeted Therapy
|April 23, 2024
PubMed

Insights

SOX9 directly interacts with YAP, promoting its nuclear translocation and tumor growth. Targeting this SOX9-YAP interaction with peptides like S-A1 inhibits YAP nuclear import and suppresses cancer progression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • YAP (Yes-associated protein) nuclear translocation is crucial for its activation and tumor progression.
  • The molecular mechanisms regulating YAP nuclear import are not fully elucidated.

Purpose of the Study:

  • To investigate the role of SOX9 in YAP activation and nuclear translocation.
  • To identify the molecular basis of SOX9-YAP interaction and its impact on cancer.

Main Methods:

  • Investigated SOX9-YAP direct interaction.
  • Identified key amino acid residues (Asp-125 of SOX9, Arg-124 of YAP) involved in binding.
  • Discovered PRMT1-catalyzed YAP dimethylation at Arg-124 (YAP-R124me2a).
  • Utilized a competitive peptide (S-A1) to disrupt SOX9-YAP interaction.

Main Results:

  • SOX9 directly interacts with YAP, promoting its nuclear translocation.
  • Specific binding between SOX9 Asp-125 and YAP Arg-124 is essential for this interaction.
  • PRMT1-mediated YAP-R124me2a enhances SOX9-YAP binding and is linked to poor cancer prognosis.
  • The peptide S-A1 effectively inhibits YAP nuclear translocation and suppresses tumor growth.

Conclusions:

  • SOX9 is a critical regulator of YAP nuclear translocation.
  • Targeting the SOX9-YAP interaction offers a potential therapeutic strategy for YAP-driven cancers.

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