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Molecular Omics
Article . 2024 . Peer-reviewed
License: CC BY
Data sources: Crossref
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Molecular Omics
Article . 2024
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YAP activation is robust to dilution

Authors: Jones, I; Arias-Garcia, M; Pascual-Vargas, P; Beykou, M; Dent, L; Chaudhuri, TP; Roumeliotis, T; +3 Authors

YAP activation is robust to dilution

Abstract

The concentration of many transcription factors exhibits high cell-to-cell variability due to differences in synthesis, degradation, and cell size. Whether the functions of these factors are robust to fluctuations in concentration, and how this may be achieved, is poorly understood. Across two independent panels of breast cancer cells, we show that the average whole cell concentration of YAP decreases as a function of cell area. However, the nuclear concentration distribution remains constant across cells grouped by size, across a 4–8 fold size range, implying unperturbed nuclear translocation despite the falling cell wide concentration. Both the whole cell and nuclear concentration was higher in cells with more DNA and CycA/PCNA expression suggesting periodic synthesis of YAP across the cell cycle offsets dilution due to cell growth and/or cell spreading. The cell area – YAP scaling relationship extended to melanoma and RPE cells. Integrative analysis of imaging and phospho-proteomic data showed the average nuclear YAP concentration across cell lines was predicted by differences in RAS/MAPK signalling, focal adhesion maturation, and nuclear transport processes. Validating the idea that RAS/MAPK and cell cycle regulate YAP translocation, chemical inhibition of MEK or CDK4/6 increased the average nuclear YAP concentration. Together, this study provides an example case, where cytoplasmic dilution of a protein, for example through cell growth, does not limit a cognate cellular function. Here, that same proteins translocation into the nucleus.

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United Kingdom
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Keywords

Cell Nucleus, 570, Tumor, Cell Cycle, Signal Transducing, Adaptor Proteins, 610, Cyclin-Dependent Kinase 4, YAP-Signaling Proteins, Breast Neoplasms, Cell Cycle Proteins, Phosphoproteins, Cell Line, Chemistry, Cell Line, Tumor, Humans, Female, Transcription Factors, Adaptor Proteins, Signal Transducing, Cell Proliferation

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
1
Average
Average
Average
Green
hybrid
Related to Research communities
Cancer Research