Where is it and how does it get there – intracellular localization and traffic of P-glycoprotein

Frontiers in Oncology

Dong eFu¹ 

[1] The University of Sydney;

关键词: P-Glycoprotein;    Recycling;    traffic;    cell polarization;    intracellular localization;    multidrug resistance in cancer;   

DOI  :  10.3389/fonc.2013.00321

来源: DOAJ

【 摘 要 】

P-glycoprotein (P-gp), an ATP-binding cassette (ABC), is able to transport structurally and chemically unrelated substrates. Overexpression of P-gp in cancer cells significantly decreases the intercellular amount of anticancer drugs, and results in multidrug resistance in cancer cells, a major obstacle in cancer chemotherapy. P-gp is mainly localized on the plasma membrane and functions as a drug efflux pump; however, P-gp is also localized in many intracellular compartments, such as endoplasmic reticulum, Golgi, endosomes and lysosomes. P-gp moves between the intracellular compartments and the plasma membrane in a microtubule-actin dependent manner. This review highlights our current understanding of 1) the intracellular localization of P-gp; 2) the trafficking and cycling pathways among the cellular compartments as well as between these compartments and the plasma membrane; and 3) the cellular factors regulating P-gp traffic and cycling. This review also presents a potential implication in overcoming P-gp-mediated multidrug resistance by targeting P-gp traffic and cycling pathways and impairing P-gp localization on the plasma membrane.

【 授权许可】

Unknown