Disease relevance of SULT1E1

• Regulation of estrogen sulfotransferase in human endometrial adenocarcinoma cells by progesterone [1].
• Expression of human estrogen sulfotransferase in Salmonella typhimurium: differences between hHST and hEST in the enantioselective activation of 1-hydroxyethylpyrene to a mutagen [2].
• It is also important to note that the status of intratumoral aromatase, 17beta-HSD type 1, EST and STS in human breast cancer tissues is variable and not necessarily correlated with each other, which suggests different potential sources of intratumoral estrogens among individual patients with breast cancer [3].
• EST and STS immunoreactivity was also correlated with various clinicopathological parameters, including prognosis to examine the biological significance of these enzymes in 113 breast carcinomas [4].
• Of the 113 invasive ductal carcinomas examined in this study, EST and STS immunoreactivity was detected in 50 and 84 cases (44.2 and 74.3%), respectively [4].

Psychiatry related information on SULT1E1

• The potential correlation between alcohol consumption and hepatic EST expression deserves further evaluation [5].
• One EST was mapped within the critical region for Rieger syndrome type 2, and three transcripts were identified in the region for the nocturnal enuresis type 1 [6].
• Fine mapping of 12 previously unassigned EST clones to individual YACs in the familial Alzheimer's disease (FAD) region of chromosome 14q24.3 [7].
• Eighty-nine volunteer subjects completed a test anxiety scale (TAS) and an effective study test (EST) at the beginning of the spring semester [8].
• These EST-related resistance mechanisms could be used in investigations into the defense mechanisms of wild species, and to provide new routes to improving the germplasm of cultivated rice [9].

High impact information on SULT1E1

• During the last five years, the development of bioinformatics and EST databases has been primarily responsible for the identification of many new chemokines and chemokine receptors [10].
• The protein is predicted to consist of 12 transmembrane domains and is 55% identical to a human EST of unknown function isolated from melanocytes and melanoma cells [11].
• More than 1.6 million human EST sequences have been deposited in public databases, making it difficult to identify ESTs that represent new genes [12].
• Using highly refined and tested algorithms for EST analysis, we have arrived at two independent estimates indicating the human genome contains approximately 120,000 genes [13].
• This is exemplified by the in silico cloning (prediction of a gene product sequence using only genomic and EST sequence data) of a new type of GTPase with two catalytic domains [12].

Chemical compound and disease context of SULT1E1

• This report describes the specific induction of hEST in human Ishikawa endometrial adenocarcinoma cells by progesterone as a model for the increases in estrogen sulfation observed in women during the secretory phase of the menstrual cycle [1].
• Transfection of expression vectors encoding human estrogen sulfotransferase and dehydroepiandrosterone (DHEA) sulfotransferase in human adrenal adenocarcinoma SW-13 cells indicates that estrogen sulfotransferase transforms estrone more specifically, whereas DHEA sulfotransferase is more specific for DHEA and pregnenolone [14].
• Regulation of SULT1E1 expression in Ishikawa adenocarcinoma cells by tibolone [15].
• We overexpressed hEST1 in Escherichia coli in fusion with GST, then purified the enzyme using a glutathione affinity column, and obtained GST-free enzyme by digestion with thrombin [16].
• Human estrogen sulfotransferase (hEST1) activities and its mRNA in various breast cancer cell lines. Effect of the progestin, promegestone (R-5020) [17].

Biological context of SULT1E1

• SULT1B1 is located on chromosome 4q13.1, nearly 100 kb downstream of SULT1E1 on the same strand [18].
• Modeling of the interactions of raloxifene in the active site of SULT1E1 indicates that both hydroxyl groups of raloxifene can be readily positioned in proximity to the sulfonyl group of 3'-phosphoadenosine 5'-phosphosulfate and the catalytically important His107 residue [19].
• Similarly, in early pregnancy (i.e. first trimester) endometrium, SULT1E1 expression was absent, although SULT1A1 and SULT1A3 expression were unaffected [20].
• Cloning and structural characterization of STE will now make it possible to study potential molecular genetic mechanisms involved in the regulation of EST in human tissues [21].
• The protein encoded by the human liver EST cDNA was 81%, 73%, and 72% identical to the amino acid sequences of guinea pig adrenocortical, bovine placental and rat liver ESTs, respectively [22].

Anatomical context of SULT1E1

• Our results with normal endometrium support in-vitro data showing that SULT1E1 expression is regulated by progesterone [20].
• In contrast, raloxifene sulfation was detectable only in secretory phase cytosols in association with SULT1E1 activity [19].
• A reduced glutathione (GSH) inducer (N-acetyl cysteine) significantly increased while a GSH depletor (buthionine sulfoxamine) significantly decreased hSULT1E1 activity, but both failed to affect the amount of hSULT1E1 protein in human hepatocyte carcinoma Hep G2 cells [23].
• I hypothesize that either STE or STD is involved in the formation of cholesterol sulfate (CS) in epidermal keratinocytes [24].
• We then performed quantitative Western blots of EST and DHEA ST in 62 samples of human jejunal mucosa [25].

Associations of SULT1E1 with chemical compounds

• T1AM, the most active thyronamine pharmacologically, was associated with the greatest SULT activity of the thyronamines tested in the liver pool and in both the expressed SULT1A3 and SULT1E1 preparations [26].
• Moreover, when estrone (which selectively inhibits expressed SULT1E1 and SULT1A3) was included in intestinal incubations, the high-affinity component of the Eadie-Hofstee plot for EE sulfation was inhibited, converting the plot from biphasic to monophasic [27].
• SULT1E1, a member of the phenol sulfotransferase family, used 3,3'-T(2) and rT(3) more readily than T(3), and also displayed the greatest specificity for T(4) among human SULTs [28].
• Liver pool (n=5) SULT activities measured with tibolone substrates reflected COS-1 expressed SULT2A1 and SULT1E1 activities [29].
• SULT1E1 was the only isoform exhibiting detectable levels of raloxifene disulfation activity [19].

Physical interactions of SULT1E1

• Human recombinant EST increased the covalent binding of [3H]N-OH-PhIP to calf thymus DNA approximately 3.5-fold in the presence of the sulfotransferase co-substrate 3'-phosphoadenosine-5'-phosphosulfate at each N-OH-PhIP concentration (1, 10 and 100 microM) (n = 6, P < 0.001) [30].

Enzymatic interactions of SULT1E1

• These results indicate that the sulfotransferase-mediated activation of the methyl-hydroxylated DMBAs is predominantly catalyzed by DHEA-steroid sulfotransferase in human liver and that TS- and TL-phenol sulfotransferases and estrogen sulfotransferase are not involved in the catalysis [31].

Regulatory relationships of SULT1E1

• The induction of SULT1E1 was inhibited by RU486 indicating a role for the progesterone receptor [15].

Other interactions of SULT1E1

• SULT1E1 displayed the lowest Km (0.2 microM) for 4-OHT sulfation and SULT2A1 the lowest (0.3 microM) for raloxifene sulfation [19].
• Although two of these enzymes, DHEA ST and one form of PST, can catalyze the sulfate conjugation of estrogens, our goal was to test the hypothesis that human liver might also contain a distinct estrogen ST (EST) [22].
• Structure and localization of the human SULT1B1 gene: neighborhood to SULT1E1 and a SULT1D pseudogene [18].
• These findings also suggest that EST and STS plays important roles in regulation of in situ estrogen production, and EST especially is a potent prognostic factor in human breast carcinoma [3].
• The induction of hEST by progesterone was inhibited by RU-486, indicating that progesterone is acting via the progesterone receptor [1].

Analytical, diagnostic and therapeutic context of SULT1E1

• Site-directed mutagenesis demonstrated that Cys83 is critical for the redox regulation of hSULT1E1 [23].
• We used the PCR to clone a human liver EST cDNA by utilizing degenerate oligonucleotide primers designed on the basis of highly conserved EST sequences in non-human species to amplify a 512 nucleotide portion of the open reading frame (ORF) with single-stranded human liver cDNA as a template [22].
• We set out to characterize immunochemically the nature and extent of individual variation in the expression of EST and DHEA ST in the human small intestine after Northern blot analysis had demonstrated that both enzymes were expressed in that tissue [25].
• Polyclonal antibodies to human EST and DHEA ST were developed, and Western blot analysis demonstrated that the antibodies were specific [25].
• These findings suggest that genetic polymorphisms of SULT1E1 are associated with increased risk and a disease free survival of breast cancer in Korean women [32].

References