Lipid Regulation of the ABCB1 and ABCG2 Multidrug Transporters

Csilla Hegedüs, Ágnes Telbisz, Tamás Hegedus, Balázs Sarkadi, Csilla Özvegy-Laczka

Research output: Chapter in Book/Report/Conference proceedingChapter

18 Citations (Scopus)


This chapter deals with the interactions of two medically important multidrug ABC transporters (MDR-ABC), ABCB1 and ABCG2, with lipid molecules. Both ABCB1 and ABCG2 are capable of transporting a wide range of hydrophobic drugs and xenobiotics and are involved in cancer chemotherapy resistance. Therefore, the exploration of their mechanism of action has major therapeutic consequences. As discussed here in detail, both ABCB1 and ABCG2 are significantly affected by various lipid compounds especially those residing in their close proximity in the plasma membrane. ABCB1 is capable of transporting lipids and lipid derivatives, and thus may alter the general membrane composition by "flopping" membrane lipid constituents, while there is no such information regarding ABCG2. Still, both ABCB1 and ABCG2 show complex interactions with a variety of lipid molecules, and the transporters are significantly modulated by cholesterol and cholesterol derivatives at the posttranslational level. In this chapter, we explore the molecular details of the direct transporter-lipid interactions, the potential role of lipid-sensor domains within the proteins, as well as the application of experimental site-directed mutagenesis, detailed structural studies, and in silico modeling for examining these interactions. We also discuss the regulation of ABCB1 and ABCG2 expression at the transcriptional level, occurring through nuclear receptors involved in lipid sensing. The better understanding of lipid interactions with these medically important MDR-ABC transporters may significantly improve further drug development and clinical treatment options.

Original languageEnglish
Title of host publicationAdvances in Cancer Research
PublisherAcademic Press Inc.
Number of pages41
Publication statusPublished - Jan 1 2015

Publication series

NameAdvances in Cancer Research
ISSN (Print)0065-230X
ISSN (Electronic)2162-5557



  • ABC multidrug transporter
  • Cholesterol
  • Membrane lipids
  • Nuclear receptors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Hegedüs, C., Telbisz, Á., Hegedus, T., Sarkadi, B., & Özvegy-Laczka, C. (2015). Lipid Regulation of the ABCB1 and ABCG2 Multidrug Transporters. In Advances in Cancer Research (pp. 97-137). (Advances in Cancer Research; Vol. 125). Academic Press Inc..