High impact information on MRP1

• Because of the structural and functional homology between Ycf1p and MRP1 and MRP2, these data support the hypothesis that GSH efflux from mammalian cells is mediated by these membrane proteins [1].
• The deduced amino acid sequence predicts that Bat1p is an ABC-type protein 1661 amino acids in length, similar to mammalian cMOAT/cMRP1 and MRP1 transporters, yeast Ycf1p, and two yeast proteins of unknown function [2].
• The energy requirements, kinetics, substrate specificity, and inhibitor profile of YCF1-mediated transport demonstrate that the vacuolar glutathione conjugate pump of yeast bears a strong mechanistic resemblance to the MRP1-encoded transporter of mammalian cells and the cognate, but as yet molecularly undefined, function of plant cells [3].
• Direct evidence is provided for the assignment of the MRP1 gene product as a protein component of the small subunit of mitochondrial ribosomes [4].
• Further studies examined the extent to which the expression of the MRP1 protein is coordinated with the expression of other mitochondrial ribosomal components coded in the nuclear and mitochondrial genomes [4].

Biological context of MRP1

• This synthetic defective phenotype suggests that the ribosomal proteins PET123 and MRP1 interact functionally with each other [5].
• The transport systems involved in the export of cellular reduced glutathione (GSH) have not been identified, although recent studies implicate a role for some of the multidrug resistance associated proteins (MRP), including MRP1 and MRP2 [1].
• ATP-dependent [3H]GSH transport was cis-inhibited by substrates of the yeast Ycf1p transporter and inhibited by 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid, probenecid, and sulfinpyrazone, inhibitors of MRP1 and MRP2, but was minimally affected by membrane potential or pH gradient uncouplers [1].
• The wild type genes MRP1 and MRP2 were cloned by transformation of the pet mutations in E795 and C167, respectively, with a recombinant plasmid library of wild type yeast genomic DNA [6].
• Increases in MRP1 gene dosage were accompanied by substantial increases in both MRP1 mRNA and protein, indicating that their accumulation was not linked to the level of expression of other mitochondrial ribosomal components [4].

Anatomical context of MRP1

• Like PET123, MRP1 encodes a component of the small subunit of mitochondrial ribosomes [5].
• Assembly of the mitochondrial membrane system. MRP1 and MRP2, two yeast nuclear genes coding for mitochondrial ribosomal proteins [6].
• CL tMRP1 expressed in Saccharomyces cerevisiae membranes displayed high-affinity ATP-dependent transport of the MRP1 substrate leukotriene C4 [7].

Associations of MRP1 with chemical compounds

• The levels of MRP1 and MRP2 mRNAs were examined in glucose-repressed cells and in cells undergoing adaptation to aerobic metabolism of ethanol [6].
• Compared with full-length MRP1, the K m for leukotriene C4 transport by CL tMRP1 was increased approximately 3-fold, while V max was not affected [7].
• We developed a functional cysteine-less version of MRP1 that provides a framework for detailed biochemical and biophysical studies [7].
• This Cys-less protein can be used for biochemical, spectroscopic and structural studies to elucidate the mechanism of drug transport by MRP1 [7].
• ATP-dependent GSH transport was not affected by either membrane potential or pH-gradient uncouplers, but was inhibited by 4, 4'-di-isothiocyanatostilbene-2,2'-disulphonate, probenecid and sulphinpyrazone, which are inhibitors of mrp1 and mrp2, mammalian homologues of the yeast YCF1 transporter [8].

Other interactions of MRP1

• However, some of the mrp1 mutations cause a non-conditional respiratory-defective phenotype in combination with certain pet123 alleles [5].
• Here we describe additional pet122 suppressors generated by mutations in a second gene which we show to be the previously identified nuclear gene MRP1 [5].

References