Disease relevance of ARR3

• In this study, we show that overexpression of Yap1 complemented the arsenite hypersensitivity of the ycf1 null mutant, but only if the ACR3 gene is functional [1].
• The hypothetical product of the ACR3 gene shows high similarity to the hypothetical membrane protein encoded by Bacillus subtilis ORF1 of the skin element and weak similarity to the ArsB membrane protein of the Staphylococcus aureus arsenical-resistance operon [2].

High impact information on ARR3

• Disruption of either the ACR3 or YCF1 gene results in sensitivity to arsenite and disruption of both genes produces additive hypersensitivity [3].
• Thus, Acr3p and Ycf1p represent separate pathways for the detoxification of arsenite in yeast [3].
• Acr3p is a plasma membrane transporter that confers resistance to arsenite, presumably by arsenite extrusion from the cells [3].
• Yap8p is demonstrated to reside in the nucleus where it mediates enhanced expression of the arsenic detoxification genes ACR2 and ACR3 [4].
• Using chromatin immunoprecipitation assays, we show that Yap8p is associated with the ACR3 promoter in untreated as well as arsenic-exposed cells [4].

Biological context of ARR3

• The presence of ACR3 together with ACR2 on a multicopy plasmid was conducive to increased arsenate resistance [5].
• Amino acid sequence analysis of Acr3p showed that this hypothetical protein has hydrophobic character with 10 putative transmembrane spans and is probably located in yeast plasma membrane [5].
• Instead, arsenite-stimulated Yap8p stabilization and transcriptional activation of ACR3 requires critical cysteine residues within Yap8p [6].
• Overexpression of the ACR3 gene confers an arsenite- but not an arsenate-resistance phenotype [2].
• Active transport of metalloids by Acr3p and Ycf1p in Saccharomyces cerevisiae and chelation by phytochelatins in Schizosaccharomyces pombe, nematodes, and plants represent distinct strategies of metalloid detoxification [7].

Anatomical context of ARR3

• The ARR2 and ARR3 genes encoding the cytoplasmic arsenate reductase and the plasma membrane arsenite transporter are functionally interchangeable in both yeast species [8].
• Yeasts extrude arsenite using Acr3p, a plasma membrane carrier protein, or sequester it in vacuoles as the glutathione conjugate using Ycf1p, an ABC transporter [9].

Associations of ARR3 with chemical compounds

• The acr3 disruptants showed wild-type sensitivity to antimony, tellurite, cadmium, and phenylarsine oxide [5].
• In Saccharomyces cerevisiae, expression of the ACR2 and ACR3 genes confers arsenical resistance [10].

Physical interactions of ARR3

• We conclude that Yap1 may compete with Yap8 for binding to the ACR3 promoter, but is unable to act as a potent activator [1].

Regulatory relationships of ARR3

• We further show that the expression of either an ACR3-lacZ promoter fusion reporter or the endogenous ACR3 gene was stimulated by the overproduction of Yap1 upon exposure to arsenite [1].

Other interactions of ARR3

• Ycf1 and Acr3 are transporters that have been previously shown to protect Saccharomyces cerevisiae cells from the toxic effects of arsenite [1].

Analytical, diagnostic and therapeutic context of ARR3

• We were also unable to detect evidence for a human homolog for the yeast arsenite efflux gene ACR3, using RT-PCR [11].

References