ABCC4

ABCC4 (ATP-binding cassette, sub-family C, member 4), also known as Multidrug Resistance Protein 4 (MRP4), is a protein that in humans is encoded by the ABCC4 gene. This protein is a member of the ATP-binding cassette (ABC) transporters superfamily, which is one of the largest and most diverse protein families involved in the transport of various molecules across extra- and intra-cellular membranes.

Structure

The ABCC4 protein is composed of multiple transmembrane domains and two nucleotide-binding domains. These domains are responsible for the transport of substrates across the cell membrane, utilizing the energy derived from ATP hydrolysis. The structure of ABCC4 is typical of the ABC transporter family, characterized by its ability to bind and hydrolyze ATP to drive the transport process.

Function

ABCC4 functions primarily as an efflux pump, transporting a wide range of substrates, including nucleoside analogs, prostaglandins, and cyclic nucleotides, out of cells. This activity is crucial in the regulation of intracellular concentrations of these molecules, impacting various physiological processes such as inflammation, immune response, and cell signaling.

Role in Drug Resistance

ABCC4 is implicated in multidrug resistance, a phenomenon where cancer cells become resistant to a variety of chemotherapeutic agents. By actively exporting drugs out of cells, ABCC4 reduces their intracellular concentrations, thereby diminishing their efficacy. This has significant implications for the treatment of cancer, as overexpression of ABCC4 can lead to treatment failure.

Clinical Significance

Mutations in the ABCC4 gene have been associated with various diseases, including Dubin-Johnson syndrome, a rare liver disorder. Additionally, ABCC4 is a target for pharmacological intervention in conditions such as cancer, HIV, and cardiovascular diseases, where modulation of its activity could enhance therapeutic outcomes.

Research Directions

Ongoing research is focused on understanding the regulatory mechanisms controlling ABCC4 expression and activity, as well as developing inhibitors that can selectively block its function. Such inhibitors have the potential to overcome drug resistance in cancer therapy and improve the efficacy of existing treatments.

Also see

• ATP-binding cassette transporter
• Multidrug resistance
• Cancer therapy
• Dubin-Johnson syndrome