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Cancer Lett. 2014 Apr 1;345(1):124-31. doi: 10.1016/j.canlet.2013.12.007. Epub 2013 Dec 11.

Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function.

Author information

1
Division of Chemotherapy, Faculty of Pharmacy, Keio University, Japan.
2
Division of Chemotherapy, Faculty of Pharmacy, Keio University, Japan. Electronic address: sugimoto-ys@pha.keio.ac.jp.

Abstract

P-glycoprotein (P-gp)/ABCB1 is a key molecule of multidrug resistance in cancer. Protein phosphatase (PP) 2A, regulatory subunit B, gamma (PPP2R3C), which is a regulatory subunit of PP2A and PP5, was identified as a binding candidate to P-gp. Immunoprecipitation-western blotting revealed that PP5 and PPP2R3C were coprecipitated with P-gp, while PP2A was not. PP5/PPP2R3C dephosphorylated protein kinase A/protein kinase C-phosphorylation of P-gp. Knockdown of PP5 and/or PPP2R3C increased P-gp expression and lowered the sensitivity to vincristine and doxorubicin. Consequently, our results indicate that PP5/PPP2R3C negatively regulates P-gp expression and function.

KEYWORDS:

Dephosphorylation; P-glycoprotein/ABCB1; PP5; PPP2R3C

PMID:
24333728
DOI:
10.1016/j.canlet.2013.12.007
[Indexed for MEDLINE]

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