Disease relevance of SNQ2

• In this study, we demonstrate that relief of estradiol toxicity in yeast cells expressing VEO requires functional PDR5 and SNQ2 genes, since a Deltapdr5 Deltasnq2 double deletion leads to an increased estradiol toxicity [1].

High impact information on SNQ2

• Some genes, such as YOR1, SNQ2, and FLR1, are clearly directly controlled by both classes of transcription factor, suggesting an important role for the corresponding membrane proteins [2].
• RNA levels of multidrug resistance genes such as PDR16, SNQ2, and PDR5 were decreased in many deletion strains [3].
• Pdr5p and two other yeast ATP-binding cassette transporters, Snq2p and Yor1p, were found to be phosphorylated on serine residues in vitro [4].
• These data underscore the role of the pleiotropic drug resistance network in regulating camptothecin toxicity and are consistent with a model of decreased intracellular concentrations of camptothecin resulting from the increased expression of the SNQ2 transporter [5].
• Furthermore, using URA3 as an estradiol-inducible reporter gene, we show that Pdr5 and Snq2, when overexpressed from high-copy plasmids, can reduce the intracellular concentration of estradiol [1].

Chemical compound and disease context of SNQ2

• Pregnenolone toxicity is more pronounced when the atf2-Delta mutation is introduced in a yeast strain devoid of the ATP-binding cassette transporters, PDR5 and SNQ2 [6].

Biological context of SNQ2

• Finally, DNA footprint analysis revealed that the SNQ2 promoter contains three binding sites for Pdr3 [7].
• We show here that a pdr1-3 mutant exhibits a PDR phenotype, including elevated resistance to the mutagen 4-nitroquinoline-N-oxide, a known substrate for Snq2 but not for Pdr5 [7].
• The substrate specificity of Pdr5p, Snq2p and Yor1p are largely, but not totally, overlapping as shown by screening the growth inhibition by 349 toxic compounds of combinatorial deletants of these three ABC genes [8].
• In a clotrimazole-resistant mutant, CTZ21, isolated from the haploid sake yeast HL69, the levels of mRNA for three major ABC transporter genes, PDR5, SNQ2, and YOR1, markedly increased [9].
• Disruption of both PDR5 and SNQ2 in a pdr1 mutant decreases the cell growth rate and reveals the presence of at least two other ATP binding cassette proteins in the 160-kDa overexpressed band that have been identified by amino-terminal microsequencing [10].

Anatomical context of SNQ2

• We have studied in detail three plasma membrane multidrug exporters: Pdr5p (TC3.A.1.205.1) and Snq2p (TC3.A.1.205.2) which share NBF-TM-NBF-TM topology as well as Yor1p (TC3.A.1.208.3) which exhibits the reciprocal TM-NBF-TM-NBF topology [8].

Associations of SNQ2 with chemical compounds

• At pH 6.4 the EC(50)'s, for all tested heavy metals were significantly low, in contrast to acidic pH conditions, in which both strains were able to grow in the presence of high concentrations of the transition metals Cu(2+), Zn(2+), and Co(2+), with the pdr5 yor1 snq2 mutant being more tolerant [11].
• The SNQ2 gene of Saccharomyces cerevisiae, which encodes an ATP binding cassette protein responsible for resistance to the mutagen 4-nitroquinoline oxide, is regulated by the DNA-binding proteins PDR1 and PDR3 [10].
• The SNQ2 protein was solubilized with n-dodecyl beta-D-maltoside from the plasma membranes of a PDR5-deleted strain and separated from the PMA1 H(+/-)ATPase by sucrose gradient centrifugation [10].
• Mucidin induced PDR5 expression, but the changes in the expression of SNQ2 were only barely detectable [12].
• PDR5 (pleiotropic drug resistance 5) deletion mutants (Deltapdr5 and Deltapdr5Deltasnq2) retained significantly higher levels of 14C-radiolabeled RH-5992 within the cells when compared to wild-type strain or single deletion mutants of SNQ2 (Deltasnq2) and YCF1 (Deltaycf1) [13].

Other interactions of SNQ2

• Furthermore, cells lacking both Yor1p and Pdr5p (but not Snq2p) showed increased accumulation of the fluorescent derivative of 1-myristoyl-2-[6-(NBD)aminocaproyl]phosphatidylethanolamine [14].
• The ATP-binding cassette multidrug transporter Snq2 of Saccharomyces cerevisiae: a novel target for the transcription factors Pdr1 and Pdr3 [7].
• In order to analyze whether membrane transporters of the facilitator or the ABC type (SNQ1 and SNQ2) have an influence on Sn2+ toxicity in yeast we used the respective mutants and compared their responses to the wild type (WT) [15].
• Epistasis analysis demonstrated that 4-NQO resistances mediated by the YRR1 and YRR1-1 alleles require the presence of the SNQ2 gene that encodes a multidrug resistance ATP binding cassette superfamily protein responsible for 4-NQO export [16].

Analytical, diagnostic and therapeutic context of SNQ2

• DNA microarray analysis revealed that all of the six mutants induce typical drug transporter genes including SNQ2 and YOR1, suggesting redundancy in regulation [17].

References