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

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• 作者：Kazuhiro Katayama ; Miho Yamaguchi ; Kohji Noguchi ; Yoshikazu Sugimoto
• 关键词：P-glycoprotein/ABCB1 ; PP5 ; PPP2R3C ; Dephosphorylation
• 刊名：Cancer Letters
• 出版年：1 April, 2014
• 年：2014
• 卷：345
• 期：1
• 页码：124-131
• 全文大小：1672 K

文摘

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.