Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

ATP-sulfurylase, cysteine synthase, homocysteine synthase, arylsulfatase and beta-cystathionase in Saccharomycopsis lipolytica are repressed on the addition of methionine, homocysteine or cysteine to the growth medium. The use of appropriate mutants enabled us to demonstrate that the synthesis of these enzymes is regulated by the system involving at least two low-molecular weight effectors--most likely cysteine and methionine (or their close derivatives).
Mol Gen Genet 1979 Jul 02
PMID:Regulation of s-amino acids biosynthesis in Saccharomycopsis lipolytica. 28 1

A gene, designated GS1, was identified by its association with a CpG island approximately 100 kb telomeric to the steroid sulfatase (STS) locus on the distal short arm of the human X chromosome. Both cDNA and genomic clones of the GS1 gene have been isolated and characterized. The cDNA clone detects a 2.3 kb transcript in human placenta and fibroblasts, and may encode a protein of 214 amino acid residues. Although sequences homologous to GS1 cDNA are present on chromosomes 1, 20, X, and Y, the functional GS1 gene is on the X chromosome. The GS1 gene appears to be non-essential, as there are no obvious clinical differences between STS deficient patients with point mutations in the STS gene, and patients with a deletion of the STS and GS1 genes. The GS1 gene is expressed from mouse-human cell hybrids containing active or inactive human X chromosomes, indicating that it escapes X inactivation. Characterization of GS1 genomic clones revealed that the gene consists of 4 exons spanning over 105 kb, with its transcriptional direction opposite to that of the STS gene. The isolation and characterization of a new gene which escapes X inactivation from distal Xp is of interest as it adds to our understanding of the structural organization of the human X chromosome and may help in providing clues regarding the mechanism of X-inactivation.
Hum Mol Genet 1992 Apr
PMID:Isolation of a new gene from the distal short arm of the human X chromosome that escapes X-inactivation. 128 67

Sodium/copper chlorophyllin (CHL) is a water-soluble derivative of chlorophyll that exhibits antimutagenic activity in several short-term genotoxicity assays and inhibits carcinogen-DNA binding in vivo. The effect of CHL pretreatment on the excretion of mutagens in the urine and feces of male Sprague-Dawley rats has been studied using the Salmonella mutagenicity assay. Animals were given 1 percent CHL in the drinking water for 2 days before administering a single dose of 2-amino-3-methylimidazo-[4,5-f]quinoline (IQ) by oral gavage. Rats pretreated with CHL had higher levels of mutagens in the urine and feces compared with animals given IQ alone; 48 hr after IQ administration, the total mutagenic dose excreted was < 4% in controls vs. 18% in rats given CHL. Mutagenicity required the presence of an activation system, was unaffected by treatment with beta-glucuronidase or arylsulfatase, and in both the urine and feces was accounted for by increased elimination of unmetabolized parent compound. The results support the view that CHL may operate in vivo as a "desmutagen" or interceptor molecule, interacting with IQ in the gut and tissues, and reducing carcinogen bioavailability.
Environ Mol Mutagen 1992
PMID:Chlorophyllin-enhanced excretion of urinary and fecal mutagens in rats given 2-amino-3-methylimidazo[4,5-f]quinoline. 139 10

The cys-3+ gene of Neurospora crassa encodes a bZIP (basic region-leucine zipper) regulatory protein that is essential for sulfur structural gene expression (e.g., ars-1+). Nuclear transcription assays confirmed that cys-3+ was under sulfur-regulated transcriptional control and that cys-3+ transcription was constitutive in sulfur controller (scon)-negative regulator mutants. Given these results, I have tested whether expression of cys-3+ under high-sulfur (repressing) conditions was sufficient to induce sulfur gene expression. The N. crassa beta-tubulin (tub) promoter was fused to the cys-3+ coding segment and used to transform a cys-3 deletion mutant. Function of the tub::cys-3 fusion in homokaryotic transformants grown under high-sulfur conditions was confirmed by Northern (RNA) and Western immunoblot analysis. The tub::cys-3 transformants showed arylsulfatase gene expression under normally repressing high-sulfur conditions. A tub::cys-3ts fusion encoding a temperature-sensitive CYS3 protein was used to confirm that the induced structural gene expression was due to CYS3 protein function. Constitutive CYS3 production did not induce scon-2+ expression under repressing conditions. In addition, a cys-3 promoter fusion to lacZ showed that CYS3 production was sufficient to induce its own expression and provides in vivo evidence for autoregulation. Finally, an apparent inhibitory effect observed with a strain carrying a point mutation at the cys-3 locus was examined by in vitro heterodimerization studies. These results support an interpretation of CYS3 as a transcriptional activator whose regulation is a crucial control point in the signal response pathway triggered by sulfur limitation.
Mol Cell Biol 1992 Apr
PMID:Production of the CYS3 regulator, a bZIP DNA-binding protein, is sufficient to induce sulfur gene expression in Neurospora crassa. 153 30

Comparison of the mutagenicity of nine isomeric benzo(a)pyrenyl [B(a)P] phenols conjugated with either sulfate or glucuronide was carried out using strain Salmonella typhimurium TA98. Of the nine conjugates tested, only B(a)P-1-sulfate was mutagenic. Accordingly, the mutagenicity of B(a)P-1-sulfate was compared with that of B(a)P and 1-hydroxybenzo(a)pyrene [B(a)P-1-OH] in the presence and absence of rat lung S9 and Aroclor-induced liver S9 with and without an NADPH-generating system. B(a)P-1-sulfate was slightly mutagenic, whereas B(a)P and the 1-hydroxy derivative were nonmutagenic when S9 fractions and NADPH were omitted. Addition of induced liver S9 with NADPH caused mutagenicity with B(a) -1-OH greater than B(a)P greater than B(a)P-1-sulfate. B(a)P-1-sulfate was the only mutagenic species when lung S9 was added. This mutagenicity did not require NADPH. Sodium sulfite, an inhibitor of arylsulfatase, decreased the mutagenicity of B(a)P-1-sulfate. These data suggest that a unique mutagenic species is generated from B(a)P-1-sulfate via arylsulfatase in rat lung.
Environ Mol Mutagen 1992
PMID:Mutagenicity of benzo(a)pyrenyl-1-sulfate in the Ames test. 157 48

Of the total number of breast cancers approx. 30-50% are hormone-dependent and estradiol is one of the main factors of cancerization. Consequently, the control of this hormone inside the cancer cell is of capital importance because it is well established that the inhibition of estradiol biosynthesis can have a positive effect on the evolution of the disease. The blockage of estradiol can be obtained by the action of anti-aromatases, anti-sulfatases, the control of the 17 beta-hydroxysteroid dehydrogenase activity or by the stimulation of the sulfotransferase which converted the estrogens in their sulfates. In breast cancer tissue estrone sulfate is quantitatively the most important source of estradiol. In the intact cell, estrone sulfatase activity is very intense in the hormone-dependent cell lines (e.g. MCF-7, T-47D) but very small activity is observed in the hormone-independent (e.g. MDA-MB-231, MDA-MB-436) cell lines. However, this activity became very strong after homogenization in the hormone-independent cells, suggesting the presence of repressive factor(s) for this enzyme or its sequestering in an inactive form, in the intact cells of these cell lines. In a series of previous studies it was found that in hormone-dependent cell lines different anti-estrogens: tamoxifen and derivatives, ICI 164,384, very significantly decrease the estradiol concentration originated from estrone sulfate, and recently it was observed that Decapeptyl (D-Trp6-gonadotropin-releasing hormone) in the presence of heparin can also decrease the conversion of estrone sulfate into estradiol. No significant effect was obtained in the presence of heparin or Decapeptyl alone. The estrone sulfatase activity can be inhibited by progesterone, the progestagen R-5020, and testosterone. In another series of recent studies the presence of very strong estrogen sulfotransferase activity has been shown in one breast cancer cell line, the MDA-MB-468. We can conclude that: (1) the control of estradiol concentration can be carried out in the breast cancer tissue itself; (2) estrone sulfate can play an important role in the bioavailability of estradiol in the breast cancer cell; and (3) as is the case for the aromatase, the control of: the estrogen sulfatase, estrogen sulfotransferase, and 17 beta-hydroxysteroid dehydrogenase can be new targets for therapeutic applications in breast cancer.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Recent data on estrogen sulfatases and sulfotransferases activities in human breast cancer. 158 Sep 21

N-[7-Nitrobenz-2-oxa-1,3-diazol-4-yl]psychosine sulfate (NBD-PS), a fluorescent analog of cerebroside sulfate (CS), was synthesized and tested as an alternative to the radiolabeled forms of CS used for assaying arylsulfatase A (ASA) in its physiological role as a cerebroside sulfate sulfohydrolase. NBD-PS simulates the natural substrate for ASA. Protocols have been developed for its use in differentiating low enzyme activities in diagnostic samples. Hydrolysis of NBD-PS is specific for ASA and optimal assay parameters were identical to those determined for CS. Differentiations between each of the major phenotypes for ASA activity were possible in the set of samples tested. One particular advantage was the ability to discriminate between individuals exhibiting arylsulfatase A pseudodeficiency and the truly deficient individuals with metachromatic leukodystrophy. Differential diagnosis was possible with fibroblast extracts by an assay that is more sensitive than procedures employing radioisotopes. Reaction products may be analyzed quantitatively by HPLC, or semiquantitatively with TLC. NBD-PS provides a simpler, safer, and more cost-effective means of performing natural substrate enzyme assays for ASA. Phenotyping with the fluorescence assay is an effective alternative to the laborious radioactive CS preparations and tissue culture loading studies that have previously been necessary.
Mol Chem Neuropathol 1991 Apr
PMID:Synthesis and characterization of NBD-PS: a fluorescent analog of cerebroside arylsulfatase A deficiency disorders. 168 Mar 31

We used adult rat hepatocytes in primary culture (HPC) as a model system to study the hepatic phase II metabolism of the anticoagulant warfarin. Hepatocytes were isolated by a collagenase perfusion technique and maintained for 24 hr in Waymouth's medium containing 0.1 mM (R)-warfarin. When HPC medium was analyzed by reverse phase high performance liquid chromatography with diode-array detection, 4'-, 6-, and 7-hydroxywarfarin were identified. Several putative conjugates were observed eluting between 13 and 18 min. Treatment of hepatocyte medium with beta-glucuronidase and sulfatase resulted in the loss of five putative conjugates and concomitant increases in 4'-, 6-, and 7-hydroxywarfarin and warfarin, suggesting that these metabolites and warfarin were conjugated. Use of the beta-glucuronidase inhibitor saccharic acid 1,4-lactone enabled the determination of the relative extents of conjugation of each metabolite by glucuronic acid and sulfate. Glucuronidation was the predominant pathway for 4'-hydroxywarfarin, whereas 6-hydroxywarfarin and warfarin occurred mainly as sulfate conjugates. In contrast, 7-hydroxywarfarin was converted to both glucuronide and sulfate conjugates. Exposure of HPC to phenobarbital resulted in a decrease in cytochrome P-450-mediated production of hydroxylated warfarin metabolites; however, an increase in the production of 8-hydroxywarfarin was observed when HPC were exposed to beta-naphthoflavone. Unique conjugation patterns were found when hydroxylated warfarins were substituted for warfarin in HPC medium. Both 7- and 8-hydroxywarfarin were converted to one sulfate and two glucuronide conjugates, whereas 4'-hydroxywarfarin was converted to a single glucuronide conjugate. A spectral library of these conjugates was used to identify the major conjugates of warfarin formed by rat HPC.
Mol Pharmacol 1992 Jan
PMID:Phase II metabolism of warfarin in primary culture of adult rat hepatocytes. 173 19

The effect of progesterone and nine synthetic progestogens on the activity rate of microsome estrone sulfatase obtained from human breast carcinoma tissues was studied. The progestogens were classified into three groups: group I with a strict inhibitor effect: demegestone and chlormadinone acetate; group II with a strict activator effect: medroxyprogesterone acetate, quingestanol acetate, lynestrenol and progesterone and group III with a nonsignificant effect: dydrogesterone, promegestone, norgestrel and danazol. Demegestone was the most potent inhibitor and medroxyprogesterone acetate and quingestanol acetate had the highest activator effect. The effect of Triton X-100, a nonionic detergent, was also tested. This detergent consistently increased the microsome estrone sulfatase activity. A comparison was made between the effects of demegestone, medroxyprogesterone acetate and danazol on estrone sulfatase activity measured with or without Triton X-100 in the incubation medium. The presence of the detergent modified the progestogen action. Our results suggest that synthetic progestogens can influence the estrone sulfatase activity measured in human breast carcinoma tissues. However, the effect of progestogens was dependent on experimental conditions. Progestogens such as demegestone and chlormadinone acetate which inhibited estrone sulfatase activity in intact preparations, can reduce the intracellular production of biological active estrogen via the sulfatase pathway.
J Steroid Biochem Mol Biol 1991 Dec
PMID:In vitro effect of synthetic progestogens on estrone sulfatase activity in human breast carcinoma. 175 97

Estrone sulfatase is an important mechanism of local synthesis of biologically active estrogens in human breast cancer. The human placental microsome and breast carcinoma mitochondrial/microsomal estrone sulfatase activity were characterized and inhibition studies performed. The Km of the placental tissue enzyme was 6.83 microM, Vmax 0.015 nmol/min/mg, and for the breast carcinoma tissue Km was 8.91 microM and Vmax 0.022 nmol/min/mg. Danazol produced a significant inhibition of estrone sulfatase (20% with 50 microM danazol). No significant inhibition was seen in the presence of aminoglutethimide, rogletimide, tamoxifen, 4-hydroxyandrostenedione, stilboestrol, or any metabolites of danazol or tamoxifen. Studies with synthetic and naturally occurring steroids demonstrated that the presence of a sulfate group at the 3 position to be the most important factor in determining inhibition, and the most potent inhibitor was 5 alpha-androstene-3 beta,17 beta-diol-3-sulfate (Ki of 2.0 microM). The naturally occurring 3-sulfated steroids all demonstrated competitive inhibition. These studies could form the basis for the design of a potent estrone sulfatase inhibitor which would have potential therapeutic activity in the management of breast cancer.
J Steroid Biochem Mol Biol 1991 Oct
PMID:Inhibition of estrone sulfatase enzyme in human placenta and human breast carcinoma. 191 38


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