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Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system.

Abstract
In this review we give an overview of the physiological functions of a group of ATP binding cassette (ABC) transporter proteins, which were discovered, and still referred to, as multidrug resistance (MDR) transporters. Although they indeed play an important role in cancer drug resistance, their major physiological function is to provide general protection against hydrophobic xenobiotics. With a highly conserved structure, membrane topology, and mechanism of action, these essential transporters are preserved throughout all living systems, from bacteria to human. We describe the general structural and mechanistic features of the human MDR-ABC transporters and introduce some of the basic methods that can be applied for the analysis of their expression, function, regulation, and modulation. We treat in detail the biochemistry, cell biology, and physiology of the ABCB1 (MDR1/P-glycoprotein) and the ABCG2 (MXR/BCRP) proteins and describe emerging information related to additional ABCB- and ABCG-type transporters with a potential role in drug and xenobiotic resistance. Throughout this review we demonstrate and emphasize the general network characteristics of the MDR-ABC transporters, functioning at the cellular and physiological tissue barriers. In addition, we suggest that multidrug transporters are essential parts of an innate defense system, the "chemoimmunity" network, which has a number of features reminiscent of classical immunology.
AuthorsBalázs Sarkadi, László Homolya, Gergely Szakács, András Váradi
JournalPhysiological reviews (Physiol Rev) Vol. 86 Issue 4 Pg. 1179-236 (Oct 2006) ISSN: 0031-9333 [Print] United States
PMID17015488 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References
  • ATP-Binding Cassette Transporters
  • Multidrug Resistance-Associated Proteins
  • Organic Anion Transporters
Topics
  • ATP-Binding Cassette Transporters (chemistry, genetics, immunology)
  • Amino Acid Sequence
  • Animals
  • Humans
  • Immune System (physiology)
  • Molecular Sequence Data
  • Multidrug Resistance-Associated Proteins (chemistry, genetics, immunology)
  • Neoplasms (immunology, physiopathology)
  • Organic Anion Transporters (chemistry, genetics, immunology)
  • Structure-Activity Relationship

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