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Yeast ABC proteins involved in multidrug resistance

Abstract

Pleiotropic drug resistance is a complex phenomenon that involves many proteins that together create a network. One of the common mechanisms of multidrug resistance in eukaryotic cells is the active efflux of a broad range of xenobiotics through ATP-binding cassette (ABC) transporters. Saccharomyces cerevisiae is often used as a model to study such activity because of the functional and structural similarities of its ABC transporters to mammalian ones. Numerous ABC transporters are found in humans and some are associated with the resistance of tumors to chemotherapeutics. Efflux pump modulators that change the activity of ABC proteins are the most promising candidate drugs to overcome such resistance. These modulators can be chemically synthesized or isolated from natural sources (e.g., plant alkaloids) and might also be used in the treatment of fungal infections. There are several generations of synthetic modulators that differ in specificity, toxicity and effectiveness, and are often used for other clinical effects.

Abbreviations

ABC:

ATP-binding cassette

AR:

activation region

BRCP:

breast cancer resistance protein

MDR:

multidrug resistance

MRP:

multidrug resistance protein

NBD:

nucleotide-binding domain

PDR:

pleiotropic drug resistance

Pgp:

P-glycoprotein

TET:

tetrandrine

TMD:

transmembrane domain

YRE:

Yap responsive element

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Correspondence to Ewa Obłąk.

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Piecuch, A., Obłąk, E. Yeast ABC proteins involved in multidrug resistance. Cell Mol Biol Lett 19, 1–22 (2014). https://doi.org/10.2478/s11658-013-0111-2

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Key words

  • ABC proteins
  • PDR subfamily
  • Saccharomyces cerevisiae
  • Multidrug resistance
  • Regulation of ABC proteins
  • Transcription factors
  • P-glycoprotein
  • Modulators of ABC proteins
  • Flavonoids
  • Phenothiazines