title: Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function.
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.
authors: Division of Chemotherapy, Faculty of Pharmacy, Keio University, Japan.
authors: Kazuhiro
authors: K
authors: Katayama
authors: Division of Chemotherapy, Faculty of Pharmacy, Keio University, Japan.
authors: Miho
authors: M
authors: Yamaguchi
authors: Division of Chemotherapy, Faculty of Pharmacy, Keio University, Japan.
authors: Kohji
authors: K
authors: Noguchi
authors: Division of Chemotherapy, Faculty of Pharmacy, Keio University, Japan. Electronic address: sugimoto-ys@pha.keio.ac.jp.
authors: Yoshikazu
authors: Y
authors: Sugimoto
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D055785:Gene Knockdown Techniques; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014750:Vincristine / Q000494:pharmacology
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006023:Glycoproteins; C525689:PPP2R3C protein, human; C021240:tissue-factor-pathway inhibitor 2; D014750:Vincristine; D004317:Doxorubicin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054648:Protein Phosphatase 2
keywords: Dephosphorylation; P-glycoprotein/ABCB1; PP5; PPP2R3C