The Influence of a Caveolin-1 Mutant on the Function of P-glycoprotein

Overview

Journal Sci Rep

Specialty Science

Date 2016 Feb 5

PMID 26843476

Citations 8

Authors

Chih-Yuan Lee

Ting-Yu Lai

Meng-Kun Tsai

Pu Ou-Yang

Ching-Yi Tsai

Shu-Wei Wu

Li-Chung Hsu

Jin-Shing Chen

Affiliations

Soon will be listed here.

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.

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