Disease relevance of SLCO6A1

• These data suggest that SLCO6A1 is a putative cancer/testis (CT) cell surface antigen of potential utility as a target for antibody-based therapy for a variety of tumor types [1].
• The E2F-pRB complex can be reconstituted in an in vitro assay using a GST-RB fusion protein isolated from Escherichia coli [2].
• Therefore, we investigated the role of GST polymorphisms in the pathogenesis of idiopathic Parkinson's disease [3].
• Since multidrug resistance and GST pi overexpression are associated with the loss of ERs in AdrR MCF7 cells, we examined several other breast cancer cell lines that were not selected for drug resistance [4].
• GST P1-1 added to the culture medium of HeLa cells augmented the protective effect of glutathione against the toxicity of adenine propenal and thymine propenal [5].

Psychiatry related information on SLCO6A1

• The five-fold variation in specific activity towards (+)-anti-BPDE observed among the different PMS may be explained by individual differences in GST Pi content or by the presence of endogenous modifiers of GST activity towards the diol-epoxide [6].

High impact information on SLCO6A1

• Cytosolic human GST exhibit genetic polymorphisms and this variation can increase susceptibility to carcinogenesis and inflammatory disease [7].
• Further, forced expression of v-H-ras in rat liver epithelial cells has been shown to enhance rat pi-class GST expression [8].
• Glutathione transferases (GST) metabolise xenobiotics, including pesticides [3].
• Mutagenesis of PABC and peptide residues was used to identify key protein-peptide interactions and quantified by isothermal calorimetry, surface plasmon resonance and GST pull-down assays [9].
• Here we show that in vitro RK phosphorylates human GST-MAPKAP kinase-2 at Thr25 in the proline-rich N-terminal region Thr222 and Ser272 in the catalytic domain and Thr334 in the C-terminal domain [10].

Chemical compound and disease context of SLCO6A1

• Expression of the human placental form of glutathione S-transferase (GST-pi) in dysplasia (53 cases), carcinoma in situ (10 cases), and invasive carcinoma (46 cases) of human uterine cervix was investigated immunohistochemically with specific anti-GST-pi rabbit antibody [11].
• GST activity towards 1-chloro-2,4-dinitrobenzene and GST-pi protein content were significantly increased in all of 4 squamous cell carcinomas examined as compared to values for normal cervical epithelia [11].
• Reduced glyoxalase activity is expected to raise intracellular levels of toxic 2-oxoaldehydes otherwise eliminated by glyoxalase I. The resulting toxicity would accompany the potentiation of cytostatic drugs, caused by inhibition of the detoxication effected by GST P1-1 [12].
• Expression of the three major cytosolic classes of glutathione S-transferases (GST; Pi, Alpha and Mu) was examined by 2D gel analysis and Western blotting of biopsies from 26 patients diagnosed with ovarian carcinoma [13].
• We previously reported that high affinity binding of 45Ca2+ to the regulatory domain of PKC beta 1, expressed as a GST fusion protein in Escherichia coli, is dependent on the presence of phosphatidylserine (PS) or 12-O-tetradecanoylphorbol-13-acetate (TPA) [14].

Biological context of SLCO6A1

• Co-immunoprecipitation and GST fusion protein binding experiments showed that the adaptor protein Shc forms a complex with the tyrosine-phosphorylated beta 4 subunit [15].
• The pKa value of the active-site Tyr-9 of GIMFhelix is 7.3 +/- 0.1, approaching the unusually low value of GST A4-4 [16].
• The theta-class GST enzymes hGSTT1-1 (human GSTTheta-1-1) and rGSTT2-2 (rat GSTTheta-2-2) share 54.3% amino acid identity and exhibit different substrate specificities [17].
• In general, GST A1-1 and GST M1-1, in contrast to GST P1-1, were more active with 4-hydroxyalkenals (products of lipid peroxidation) than with base propenals [5].
• GST estimates (a measure of genetic differentiation inversely proportional to gene flow) from mtDNA sequences vary between 0.13 and 0.39 and are typically five times greater than GST estimates from STR loci (0.05-0.08) [18].

Anatomical context of SLCO6A1

• The exclusive expression of human GST mRNA in the testis was confirmed by RT-PCR [19].
• In each of these cell lines we found an inverse association between GST pi expression and ER content [4].
• Glutathione transferase (GST) of human erythrocytes, while homogeneous upon electrophoresis, varied more than sixfold in amount in individuals [20].
• The EBNA2-TAT peptide blocked EBNA2-CBF1 interaction in an in vitro GST affinity assay and labeling with fluorescein confirmed that the EBNA2-TAT peptide efficiently entered cultured B cells [21].
• Upon activation of Jurkat T cells via the TCR-CD3 complex, we find that high-affinity binding of Cbl requires the N-terminal SH3 domain of GST-Grb2 fusion protein but after cross-linking of the TCR-CD3 and CD4 receptors, Cbl binds equally to its SH2 domain [22].

Associations of SLCO6A1 with chemical compounds

• The final product of the sequential redesign of GST A1-1, mutant GIMFhelix, had a 300-fold increase in catalytic efficiency with nonenal and a >10 times decreased activity with 1-chloro-2,4-dinitrobenzene [16].
• The catalytic efficiency of GST P1-1 with adenine propenal (kcat/Km = 7.7 x 10(5) M-1.s-1) is the highest so far reported with any substrate for this enzyme [5].
• This GST is highly abundant in the parasite, its activity was found to be increased in chloroquine-resistant cells, and it has been shown to act as a ligandin for parasitotoxic hemin [23].
• GST P1-1 was particularly active in catalyzing the reactions with the propenal derivatives, and adenine propenal was the substrate giving the highest activity [5].
• Results from coprecipitation experiments using anti-CrkL and GST-fusion proteins suggest that CrkL binds to WASP through its SH3 domain and that the binding was not affected by WASP tyrosine phosphorylation [24].

Analytical, diagnostic and therapeutic context of SLCO6A1

• We have now used GST fusion protein experiments, coimmunoprecipitations and Far Western blot analyses to demonstrate direct binding between U1A and the 160-kD subunit of cleavage-polyadenylation specificity factor (CPSF) [25].
• Tyrosyl phosphorylated proteins were detected by Western blots and the interaction of c-src with the c-terminus of alpha subunit of Ca(2+) channel was determined by a GST pull-down assay [26].
• GST pull-down and immunoprecipitation assays revealed that ATF6(N) bound to SREBP2(N) [27].
• We mapped the GST pi gene to human chromosome 11q13 by in situ hybridization [4].
• GST P1-1 introduced into Hep G2 cells by electroporation was similarly found to increase their resistance to acrolein [5].

References