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Updated: Feb 5, 2026
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A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
Published on: April 29, 2022
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Development of a yeast-based system to identify new hBRAFV600E functional interactors
Simone Lubrano1,2,3, Laura Comelli2, Chiara Piccirilli2
1Oncogenomics Unit, Core Research Laboratory, ISPRO, Pisa, Italy.
Oncogene
|September 22, 2018
Summary
Researchers used yeast to discover SMIM10, a protein that reduces BRAFV600E oncogene levels in melanoma. Overexpressing SMIM10 inhibits cancer cell growth and improves patient prognosis, highlighting its therapeutic potential.
Area of Science:
- Molecular Biology
- Cancer Research
- Yeast Genetics
Background:
- The BRAFV600E oncoprotein is a key driver in melanoma, but its regulatory network is poorly understood.
- Identifying novel regulators of BRAFV600E is crucial for developing targeted cancer therapies.
Purpose of the Study:
- To utilize yeast Saccharomyces cerevisiae as a model system to study human BRAFV600E regulation.
- To identify novel human genes that modulate BRAFV600E activity and expression.
Main Methods:
- Functional screening of a human cDNA library in yeast under conditions of BRAFV600E expression.
- Assessing BRAFV600E activity by its ability to rescue growth defects in yeast HOG pathway mutants.
- Evaluating the effect of candidate genes on BRAFV600E levels and melanoma cell phenotypes.
Main Results:
- Human BRAFV600E was found to be active in yeast, rescuing growth in osmotic stress conditions.
- A functional screen identified SMIM10 as a suppressor of BRAFV600E-induced toxicity in yeast.
- SMIM10 overexpression in melanoma cells downregulated BRAFV600E, induced senescence, and increased sensitivity to vemurafenib.
- Higher SMIM10 levels correlated with better prognosis in TCGA melanoma patient data.
Conclusions:
- Saccharomyces cerevisiae is a valuable model for studying BRAFV600E regulation and identifying interacting proteins.
- SMIM10 acts as an oncosuppressor in melanoma by downregulating BRAFV600E, presenting a potential therapeutic target.
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