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Related Experiment Video

Updated: Jun 13, 2025

Automated Acoustic Dispensing for the Serial Dilution of Peptide Agonists in Potency Determination Assays
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YAP activation is robust to dilution.

Ian Jones1, Mar Arias-Garcia1, Patricia Pascual-Vargas1

  • 1Chester Beatty Laboratories, Division of Cancer Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK. dmcbijo@ucl.ac.uk.

Molecular Omics
|September 16, 2024
PubMed
Summary
This summary is machine-generated.

Cell size variations do not affect YAP protein

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Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Transcription factor concentration varies significantly between cells due to synthesis, degradation, and cell size.
  • The robustness of transcription factor function to concentration fluctuations and the mechanisms behind it are not well understood.

Purpose of the Study:

  • To investigate how cell size affects the concentration and nuclear translocation of the YAP transcription factor.
  • To explore the mechanisms regulating YAP concentration and translocation across different cell types and conditions.

Main Methods:

  • Quantified whole-cell and nuclear YAP concentration in breast cancer cells using imaging.
  • Analyzed YAP concentration in relation to cell area, DNA content, and cell cycle markers (CycA/PCNA).
  • Integrated imaging with phospho-proteomic data and used chemical inhibitors (MEK, CDK4/6) to study YAP regulation.

Main Results:

  • Whole-cell YAP concentration decreased with increasing cell area, but nuclear YAP concentration remained constant across cell sizes.
  • YAP concentration correlated with DNA content and cell cycle markers, suggesting cell cycle synthesis offsets dilution.
  • RAS/MAPK signaling, focal adhesion maturation, and nuclear transport predicted nuclear YAP levels; MEK and CDK4/6 inhibition increased nuclear YAP.

Conclusions:

  • YAP nuclear translocation is robust to changes in whole-cell concentration caused by cell size variations.
  • Cell cycle-dependent synthesis and signaling pathways (RAS/MAPK) regulate YAP nuclear import, maintaining function despite cell growth.
  • This study demonstrates a mechanism where protein translocation into the nucleus is maintained despite cytoplasmic dilution.