title: The influence of a caveolin-1 mutant on the function of P-glycoprotein.
abstract: The genetic heterogeneity in cancer cells has an increased chance in the acquisition of new mutant such as drug-resistant phenotype in cancer cells. The phenotype of drug resistance in cancer cells could be evaluated by the number or function of drug transporters on cell membranes, which would lead to decreased intracellular anti-cancer drugs concentration. Caveolae are flask-shaped invaginations on cell membrane that function in membrane trafficking, endocytosis, and as a compartment where receptors and signaling proteins are concentrated. Caveolin-1 (CAV1) is the principal structural protein of caveolae and closely correlates with multidrug resistance in cancer cells. In a systematic study of the ubiquitin-modified proteome, lysine 176 of CAV1 was identified as a potential post-translational modification site for ubiquitination. In this article, we identified a mutation at lysine 176 to arginine (K176R) on CAV1 would interfere with the biogenesis of caveolae and broke the interaction of CAV1 with P-glycoprotein. Functional assays further revealed that K176R mutant of CAV1 in cancer cells increased the transport activity of P-glycoprotein and decreased the killing ability of anti-cancer drugs in non-small-cell lung cancer cell lines.
authors: Department of Surgery, No. 7 Chung San South Road, Taipei 10002, Taiwan.|Institute of Molecular Medicine, College of Medicine, National Taiwan University, No. 1 Jen-Ai Road, Sec. 1, Taipei 10002, Taiwan.
authors: Chih-Yuan
authors: CY
authors: Lee
authors: Institute of Molecular Medicine, College of Medicine, National Taiwan University, No. 1 Jen-Ai Road, Sec. 1, Taipei 10002, Taiwan.
authors: Ting-Yu
authors: TY
authors: Lai
authors: Department of Surgery, No. 7 Chung San South Road, Taipei 10002, Taiwan.
authors: Meng-Kun
authors: MK
authors: Tsai
authors: Department of Medical Research, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei 10002, Taiwan.
authors: Pu
authors: P
authors: Ou-Yang
authors: Department of Medical Research, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei 10002, Taiwan.
authors: Ching-Yi
authors: CY
authors: Tsai
authors: Department of Surgery, No. 7 Chung San South Road, Taipei 10002, Taiwan.
authors: Shu-Wei
authors: SW
authors: Wu
authors: Institute of Molecular Medicine, College of Medicine, National Taiwan University, No. 1 Jen-Ai Road, Sec. 1, Taipei 10002, Taiwan.
authors: Li-Chung
authors: LC
authors: Hsu
authors: Department of Surgery, No. 7 Chung San South Road, Taipei 10002, Taiwan.
authors: Jin-Shing
authors: JS
authors: Chen
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism*; D051242:Caveolin 1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D055503:Protein Multimerization; D011499:Protein Processing, Post-Translational; D021381:Protein Transport
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; C495540:CAV1 protein, human; D051242:Caveolin 1; D004317:Doxorubicin; D008239:Lysine