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Updated: May 4, 2026
10:17
A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
Published on: April 29, 2022
1.8K
Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and
Kazuhiro Katayama1, Miho Yamaguchi1, Kohji Noguchi1
1Division of Chemotherapy, Faculty of Pharmacy, Keio University, Japan.
Cancer Letters
|December 17, 2013
Summary
Protein phosphatase 5 (PP5) and its regulatory subunit PPP2R3C negatively regulate P-glycoprotein (P-gp) expression and function, impacting cancer multidrug resistance. This finding offers new insights into overcoming drug resistance in cancer therapy.
Area of Science:
- Molecular Biology
- Biochemistry
- Cancer Research
Background:
- P-glycoprotein (P-gp/ABCB1) is crucial in cancer multidrug resistance.
- Identifying P-gp regulators is key to overcoming treatment resistance.
Purpose of the Study:
- To investigate the interaction between P-gp and protein phosphatase 2A, regulatory subunit B, gamma (PPP2R3C).
- To elucidate the role of PP5 and PPP2R3C in regulating P-gp expression and function.
Main Methods:
- Immunoprecipitation-western blotting to detect protein interactions.
- Functional assays involving knockdown of PP5 and PPP2R3C.
- Assessment of P-gp expression and cellular sensitivity to chemotherapy drugs.
Main Results:
- PP5 and PPP2R3C were found to directly bind and dephosphorylate P-gp.
- Knockdown of PP5 and/or PPP2R3C led to increased P-gp expression.
- Reduced sensitivity to vincristine and doxorubicin was observed upon PP5/PPP2R3C knockdown.
Conclusions:
- PP5 and PPP2R3C negatively regulate P-gp expression and function.
- These phosphatases represent potential therapeutic targets for overcoming P-gp-mediated multidrug resistance in cancer.
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