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

Kazuhiro Katayama, Miho Yamaguchi, Kohji Noguchi, Yoshikazu Sugimoto

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)124-131
Number of pages8
JournalCancer Letters
Volume345
Issue number1
DOIs
Publication statusPublished - 2014 Apr 1

Keywords

  • Dephosphorylation
  • P-glycoprotein/ABCB1
  • PP5
  • PPP2R3C

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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