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)

Leishmania major promastigotes, when grown in the presence of tunicamycin (TM), produced a plasma membrane-bound, proteolytically active gp63 with a lower molecular weight than the native glycoprotein. However, this lower molecular weight form of gp63 continued to be recognized by concanavalin A (Con A), suggesting that inhibition of N-linked glycosylation was not complete. Metabolic labeling of gp63, using [35S]methionine, demonstrated that in the range of 5-10 micrograms ml-1 TM, only the lower molecular weight form was synthesized, suggesting that inhibition was complete and that lectin binding was likely due to the GPI anchored sugars. Removal of the oligosaccharides from L. major and L. mexicana amazonensis promastigotes using endoglycosidase F, caused the gp63 molecular weight to decrease to the same value observed in the presence of TM, once again without affecting the proteolytic activity. However, this deglycosylated enzyme continued to bind Con A until subsequently treated with periodate. The latter oxidation reaction resulted in complete loss of Con A binding without inhibiting the protease activity or the substrate specificity of gp63. Further investigations revealed that both glycosylated and deglycosylated gp63 were resistant to proteolytic digestion by either autolysis or cathepsin D. These findings indicate that the N-linked oligosaccharides of gp63 are not essential for folding, transport, maintenance of enzyme activity or resistance to proteolysis.
Mol Biochem Parasitol 1994 Jan
PMID:An investigation into the significance of the N-linked oligosaccharides of Leishmania gp63. 818 21

The presence of the zymogen of cathepsin D in human milk was detected using antibodies specific for the proenzyme and by the proteolytic activity at low pH. The antibodies were raised against a synthetic propeptide of human cathepsin D and were tested using immunoprecipitations and western blots of samples from different breast cancer cell lines as well as cytosol fractions of human breast cancer tissues. In all experiments these antibodies recognized specifically procathepsin D. Procathepsin D from human milk was partially activated at low pH. The activity was monitored using hemoglobin 14C proteolytic assay, and it was abolished by pepstatin A--a specific inhibitor of aspartic proteinases. Western blots did not reveal presence of cathepsin B or cathepsin H. These data indicate specific secretion of cathepsin D in human breast milk.
Biochem Mol Biol Int 1993 Aug
PMID:Human breast milk contains procathepsin D--detection by specific antibodies. 822 Feb 41

An enzyme which catalyzes the conversion of proendothelin-1 to the potent vasoconstrictor peptide endothelin-1 has been identified in the detergent extract of primary porcine aortic endothelial cell membranes. Partial purification was accomplished by anion exchange and Con A affinity chromatography. The enzyme was active at pH 4 and was inhibited by 100 nM peptstatin A. Hydrolysis products of proendothelin-1 were characterized by bioassay, RIA, HPLC and molecular mass analysis. Comparisons to cathepsin D and renin demonstrated that the endothelin converting enzyme activity from the porcine aortic endothelial cells was unrelated to the known enzymes. These results suggest that the processing of proendothelin-1 by endothelial cells involves a novel pepstatin-sensitive aspartyl protease.
Biochem Mol Biol Int 1993 Mar
PMID:Identification of a novel aspartyl endothelin converting enzyme in porcine aortic endothelial cells. 849 May 80

17 beta-Estradiol (E2) induces cathepsin D mRNA levels and intracellular levels of immunoreactive protein in MCF-7 human breast cancer cells. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) alone does not affect cathepsin D gene expression in this cell line; however, in cells cotreated with TCDD and E2, TCDD inhibited E2-induced cathepsin D mRNA levels, the rate of gene transcription, and levels of immunoreactive protein. The inhibitory responses were observed within 30 to 120 min after the cells were treated with TCDD. TCDD also inhibited E2-induced secreted alkaline phosphatase activity in aryl hydrocarbon (Ah)-responsive MCF-7 and wild-type mouse Hepa 1c1c7 cells cotransfected with the human estrogen receptor (hER) and the pBC12/S1/pac plasmid, which contains the 5' promoter region (-296/+57) of the cathepsin D gene and an alkaline phosphatase reporter gene. The E2-responsive ER/Sp1 sequence (-199 to -165) in the cathepsin D 5' region contains an imperfect GTGCGTG (-175/-181) xenobiotic responsive element (XRE); the role of this sequence in Ah responsiveness was investigated in gel electrophoretic mobility shift assays and with plasmid constructs containing a wild-type ER/Sp1 oligonucleotide or a mutant ER/Sp1-"XRE" oligonucleotide containing two C-->A mutations in the XRE sequence (antisense strand). In plasmid constructs which contained a chloramphenicol acetyltransferase reporter gene and the wild-type ER/Sp1 promoter sequence, E2-induced chloramphenicol acetyltransferase activity and mRNA levels were inhibited by TCDD whereas no inhibition was observed with the mutant ER/Sp1-"XRE" plasmids. Electrophoretic mobility shift assays showed that the nuclear or transformed cytosolic Ah receptor complex blocked formation of the ER-Sp1 complex with the wild-type but not the ER/Sp1 mutant oligonucleotide. Moreover, incubation of the wild-type bromodeoxyuridine-substituted ER/Sp1 oligonucleotide with the nuclear Ah receptor complex gave a specifically bound cross-linked 200-kDa band. These data demonstrate that Ah receptor-mediated inhibition of E2-induced cathepsin D gene expression is due to disruption of the ER-Sp1 complex by targeted interaction with an overlapping XRE.
Mol Cell Biol 1995 Dec
PMID:Molecular mechanism of inhibition of estrogen-induced cathepsin D gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in MCF-7 cells. 852 36

Estrogen receptor positive ovarian cancer is often refractile to antiestrogen therapy. Here we describe the SKOV3 human ovarian carcinoma cell line as an in vitro model for estrogen and antiestrogen resistant ovarian cancer. While SKOV3 cells expressed estrogen receptor (ER) mRNA and protein at a similar level as the estrogen responsive T47D breast carcinoma cell line, their growth was not responsive to estradiol (E2) and was not inhibited by the antiestrogens OH-tamoxifen and ICI 164,384. The ER in SKOV3 cells was normal with respect to apparent Kd for binding with E2, E2 regulation of a transiently transfected ERE driven reporter gene, and E2 stimulation of expression of the early growth response genes c-myc and c-fos. However, the SKOV3 cells exhibited no expression of the progesterone receptor gene (PR) even after addition of E2, and the protein products of the estrogen responsive genes HER-2/neu and cathepsin D were expressed at constitutive levels that were not regulated by E2. Therefore, estrogen resistance in these cells may be a result of constitutive expression and loss of E2 regulation of selected growth regulatory gene products rather than a defect in estrogen activation of ER as a transcriptional regulator.
J Steroid Biochem Mol Biol 1995 Dec
PMID:SKOV3 ovarian carcinoma cells have functional estrogen receptor but are growth-resistant to estrogen and antiestrogens. 854 Dec 24

Retinoic acid (RA) regulation of human cathepsin D (cath D) gene expression was investigated in this study. RA enhanced cath D mRNA levels in a concentration-dependent manner in MCF-7 human breast carcinoma cells. RA regulation of cath D mRNA levels was predominantly transcriptional because RA also increased cath D gene core promoter activity. Upon further characterization of the core promoter we localized RA responsive region to proximal 112-bp. The proximal 112-bp region of cath D gene promoter harbours several retinoid response element (RARE)-like sequences. In gel shift experiments the sequence between -100 and -74 nucleotides in the CD112 region carrying imperfect direct repeat and a palindrome competed with RARE for binding to RAR/RXRs. These sequences, however, exhibited binding to protein complexes which could not be competed with unlabeled RARE or up-shifted with RAR/RXR-specific antibodies. We conclude that RA predominantly regulates cath D gene expression from the proximal 112-bp of the promoter region, but this regulation appears indirect.
J Steroid Biochem Mol Biol 1996 Mar
PMID:Retinoid regulation of human cathepsin D gene expression. 863 64

A digestive proteinase was isolated from larval extracts of Tribolium castaneum. The enzyme was partially purified using gel-filtration and ion-exchange chromatography. It is an acidic proteinase with a maximal activity at pH 3. Considering its inhibition by Pepstatin A, plus its selectivity to hydrolyze hemoglobin but not bovine serum albumin, it was classified as Cathepsin D proteinase. Its relative molecular weight is 22 kDa and it shows a high sensitivity to temperature. Unlike other cathepsin D found in animals, this enzyme is free of carbohydrate, and its activity is not affected by the presence of different anions which are known to affect the activity of plant aspartic proteinases.
Insect Biochem Mol Biol 1996 Jan
PMID:Purification and characterization of a digestive cathepsin D proteinase isolated from Tribolium castaneum larvae (Herbst). 867 82

Glucocorticoids have been used in the treatment of a number of diseases where immunological intolerance plays a predominant role. Since immunological intolerance points to the involvement of lysosomal enzymes and glucocorticoids are known to affect their activities, we have attempted to study the effect of these steroids on cardiac and renal enzymes. Dexamethasone, a glucocorticoid, is administered subcutaneously to male Wistar rats at a dosage of 2.5 mg/kg/week on alternate days for two weeks. After withdrawing the steroid, the animals are monitored for one week to oversee the recovery process. Total and free activities of glycohydrolases and cathepsins in serum, heart and kidney are assayed on the days 4, 8, 12, 16 of dexamethasone administration and also on days 4 and 8 following discontinuation of the steroid. During dexamethasone administration, a significant decrease in both the free and total activities of beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-galactosidase, alpha-galactosidase, alpha-mannosidase, cathepsin B and cathepsin D are observed in heart and kidney, but the enzyme levels are shown to increase in serum. On withdrawal of the steroid, the activities of beta-glucuronidase, beta-N-acetyl glucosaminidase, beta-galactosidase are found to be increased in heart and kidney, whereas, the activity of alpha-mannosidase remains within normal values. Thus, it could be seen that dexamethasone alters the pattern of glycohydrolases and cathepsins, which are involved in protein degradation.
Mol Cell Biochem 1996 Jan 26
PMID:Alterations in certain lysosomal glycohydrolases and cathepsins in rats on dexamethasone administration. 871 30

Estrogens play an important role in breast cancer and the effect of estrogen on growth of breast cancer cells has been extensively studied. However, only little information is available about the response of normal breast epithelial cells to estrogen, mainly due to the difficulties in establishing estrogen receptor (ER)-positive human breast epithelial cells in culture. We have stably transfected the human estrogen receptor (hER) wt cDNA into the ER-negative, spontaneously immortalized human breast epithelial cell line, HMT-3522S1, in order to develop a model for studying the effect of estrogen on nonmalignant human breast epithelial cells. Characterization of the transfected clone F9 confirmed incorporation of the estrogen receptor gene in the genome, expression of hER mRNA and hER protein. However, proliferation of F9 cells was inhibited by both estradiol (E2) and tamoxifen, whereas the pure antiestrogen ICI 182,780 had no effect on cell proliferation. This seems paradoxical since E2 stimulated the expression of the endogenous genes, TGF-alpha, cathepsin D, and alpha1-antitrypsin. In breast cancer cell lines, high expression of these genes is correlated to estrogen-stimulated cell proliferation. The spontaneously immortalized HMT-3522S1 cells transfected with wt ER cDNA behave similarly to cell lines from nonmalignant breast tissue immortalized by carcinogens and transfected with mutated ER cDNA as described by others. The discrepancy between growth inhibition and induction of positive growth factors by E2 indicates that either ER-positive nonmalignant breast epithelial cells are growth-inhibited by E2 in contrast to malignant cells or that introduction of the ER into ER-negative cells is not sufficient for restoring "normal' estrogen responsiveness.
Mol Cell Endocrinol 1996 May 17
PMID:Characterization of a nontumorigenic human breast epithelial cell line stably transfected with the human estrogen receptor (ER) cDNA. 879 53

We examined the nature of the activation of cathepsin D by polyanionic compounds. Tripolyphosphate, a model compound for polyanions, decreased the Km value of porcine cathepsin D for bovine serum albumin without affecting VMAX. Half-maximal activation was achieved at 0.2 mM free tripolyphosphate. Electrophoretic mobility of cathepsin D decreased as the tripolyphosphate concentration was increased, and the enzyme had no net charge at 50 mM triP. The concentration for the half-maximal mobility change of cathepsin D (0.18 mM) was similar to that for half-maximal activation. These results suggest that tripolyphosphate increased affinity of the enzyme for its substrate by cancelling positive charges on cathepsin D and thus decreasing the electrostatic repulsion.
Biochem Mol Biol Int 1996 Jul
PMID:Activation of cathepsin D by polyanionic compounds. 884 38


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