Structure and function of BCRP, a broad specificity transporter of xenobiotics and endobiotics

Area of Science:

• Biochemistry
• Pharmacology
• Genetics

Background:

• Breast cancer resistance protein (BCRP) is an efflux transporter linked to multidrug resistance.
• Its physiological significance was previously uncertain due to a lack of clear phenotypes in genetically modified models.
• Endogenous substrates for BCRP are known, but its broader physiological role remained debated.

Purpose of the Study:

• To summarize current knowledge on BCRP transporter function at molecular, tissue, and systemic levels.
• To explore BCRP's role in both physiological processes and disease states.
• To review common experimental methods for identifying BCRP substrates and inhibitors.

Main Methods:

• High-performance genetic analyses to investigate BCRP relevance.
• Fine-resolution tissue expression data analysis.
• Quantitative proteomics for absolute interaction frameworks.
• Review of experimental procedures for substrate and inhibitor identification.

Main Results:

• BCRP's role in drug resistance and pharmacokinetics is well-established.
• Advanced genetic and proteomic analyses reveal unexpected physiological relevance.
• Quantitative proteomics provides frameworks for modeling interactions and understanding species differences.

Conclusions:

• BCRP plays a significant role in physiology and disease beyond drug resistance.
• Modern analytical techniques are crucial for fully understanding BCRP's complex functions.
• Further research using these methods will enhance insights into interindividual and species variations in BCRP activity.