Cited by 761Drug Transport and Resistance MechanismsPharmacogenetics and Drug MetabolismAntibiotic Resistance in Bacteria

Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins

Deeley, Roger G., Westlake, Christopher, Cole, Susan P. C.·2006·Physiological Reviews

Abstract

Multidrug Resistance Proteins (MRPs), together with the cystic fibrosis conductance regulator (CFTR/ABCC7) and the sulfonylurea receptors (SUR1/ABCC8 and SUR2/ABCC9) comprise the 13 members of the human "C" branch of the ATP binding cassette (ABC) superfamily. All C branch proteins share conserved structural features in their nucleotide binding domains (NBDs) that distinguish them from other ABC proteins. The MRPs can be further divided into two subfamilies "long" (MRP1, -2, -3, -6, and -7) and "short" (MRP4, -5, -8, -9, and -10). The short MRPs have a typical ABC transporter structure with two polytropic membrane spanning domains (MSDs) and two NBDs, while the long MRPs have an additional NH2-terminal MSD. In vitro, the MRPs can collectively confer resistance to natural product drugs and their conjugated metabolites, platinum compounds, folate antimetabolites, nucleoside and nucleotide analogs, arsenical and antimonial oxyanions, peptide-based agents, and, under certain circumstances, alkylating agents. The MRPs are also primary active transporters of other structurally diverse compounds, including glutathione, glucuronide, and sulfate conjugates of a large number of xeno- and endobiotics. In vivo, several MRPs are major contributors to the distribution and elimination of a wide range of both anticancer and non-anticancer drugs and metabolites. In this review, we describe what is known of the structure of the MRPs and the mechanisms by which they recognize and transport their diverse substrates. We also summarize knowledge of their possible physiological functions and evidence that they may be involved in the clinical drug resistance of various forms of cancer.

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Crossref · 10.1152/physrev.00035.2005

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  • OATPs belong to the SLCO transporter gene superfamily and are the primary transporters for the influx of conjugated steroids, while MDR proteins belonging to the ABC transporters are the primary transporters for the efflux of conjugated steroids.

    “Organic anion-transporting polypeptides (OATPs) belong to the solute carrier organic anion (SLCO) transporter gene superfamily and are the primary transporters for the influx of conjugated steroids, while multi drug resistant (MDR) proteins belonging to the ATP-binding cassette (ABC) transporters are the primary transporters for the efflux of conjugated steroids (Deeley et al., 2006, Mueller et al”

    From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Deeley et al., 2006

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Authors
Deeley, R. G., Westlake, C., & Cole, S. P. C.
Affiliations
Queen's University (CA)
Venue
Physiological Reviews
Published
2006-07
Volume
86
Issue
3
Pages
849-899
ISSN
  • 0031-9333 (ISSN-L)
  • 1522-1210
OpenAlex
W2151625463
Cited by
761
References
584
Citations by year
2026: 5 · 2025: 14 · 2024: 17 · 2023: 19 · 2022: 26 · 2021: 33 · 2020: 21 · 2019: 20 · 2018: 26 · 2017: 42 · 2016: 40 · 2015: 42 · 2014: 55 · 2013: 51 · 2012: 54
FWCI
5.61
Type
journal article
Language
en
Open access
closed
Locations
  • Physiological Reviews (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
Keywords
multidrug resistance protein, ABC transporters, ABCB subfamily, drug efflux, xenobiotic transport, substrate recognition, nucleotide-binding domain, transmembrane domain, drug resistance, cancer chemotherapy resistance, glutathione conjugates, glucuronide conjugates, sulfate conjugates, CFTR, sulfonylurea receptor
MeSH terms
Amino Acid Sequence, Animals, Biological Transport, Humans, Mammals, Molecular Sequence Data, Xenobiotics, Protein Structure, Tertiary, ATP-Binding Cassette Transporters

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