The Role of pVHL in Regulating EGFR Degradation in Kidney Cancer
Author Information
Author(s): Zhou Liang, Yang Haifeng
Primary Institution: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America
Hypothesis
pVHL promotes the poly-ubiquitylation and degradation of activated EGFR independently of c-Cbl.
Conclusion
pVHL limits EGFR signaling by promoting c-Cbl-independent poly-ubiquitylation of the activated receptor, leading to its degradation by the proteasome.
Supporting Evidence
- VHL-deficient ccRCC cells showed higher stability of activated EGFR compared to VHL-expressing cells.
- Proteasomal inhibitors increased the half-life of activated EGFR in both VHL-expressing and VHL-deficient cells.
- c-Cbl suppression significantly stabilized activated EGFR in VHL-deficient cells but not in VHL-expressing cells.
- pVHL was found to promote poly-ubiquitylation of activated EGFR independently of c-Cbl.
Takeaway
This study shows that a protein called pVHL helps to break down another protein, EGFR, which can cause cancer if it stays active for too long.
Methodology
The study involved comparing the stability of activated EGFR in VHL-expressing and VHL-deficient ccRCC cells using various inhibitors and shRNA constructs.
Limitations
The study primarily focused on specific cell lines and may not fully represent all kidney cancer types.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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