The Pharmacological and Physiological Role of Multidrug-Resistant Protein 4

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 354; no. 3; pp. 358 - 375
• Main Authors: Wen, Jiagen, Luo, Jianquan, Huang, Weihua, Tang, Jie, Zhou, Honghao, Zhang, Wei
• Format: Journal Article
• Language: English
• Published: United States 01.09.2015
• Subjects: Animals; ATP-Binding Cassette Transporters - metabolism; Biological Transport - physiology; Humans; Multidrug Resistance-Associated Proteins - metabolism; Neoplasms - metabolism; Pharmaceutical Preparations - metabolism; Signal Transduction - physiology
• ISSN: 0022-3565; 1521-0103
• DOI: 10.1124/jpet.115.225656

Multidrug-resistant protein 4 (MRP4), a member of the C subfamily of ATP-binding cassette transporters, is distributed in a variety of tissues and a number of cancers. As a drug transporter, MRP4 is responsible for the pharmacokinetics and pharmacodynamics of numerous drugs, especially antiviral drugs, antitumor drugs, and diuretics. In this regard, the functional role of MRP4 is affected by a number of factors, such as genetic mutations; tissue-specific transcriptional regulations; post-transcriptional regulations, including miRNAs and membrane internalization; and substrate competition. Unlike other C family members, MRP4 is in a pivotal position to transport cellular signaling molecules, through which it is tightly connected to the living activity and physiologic processes of cells and bodies. In the context of several cancers in which MRP4 is overexpressed, MRP4 inhibition shows striking effects against cancer progression and drug resistance. In this review, we describe the role of MRP4 more specifically in both healthy conditions and disease states, with an emphasis on its potential as a drug target.