Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene that encodes a proteoglycan peptide core rich in serine and glycine (SG-PG) is selectively expressed by hematopoietic cells that store in their cytoplasmic granules negatively charged proteoglycans bound ionically to numerous positively charged proteins. With deletion analysis, a negative transcription regulatory element was located between residues -250 and -190 of the 5'-flanking region of the mouse SG-PG gene, and a positive regulatory element was located between residues -118 and -81. The negative regulatory element was dominantly active in fibroblasts that do not express the SG-PG gene whereas the positive regulatory element was dominantly active in hematopoietic cells that do express the SG-PG gene. Site-directed mutagenesis was used to demonstrate that the proximal element within the gene's atypical promoter resided between residues -40 and -20. As assessed by gel mobility shift analyses, the nuclei of rat basophilic leukemia-1 cells and rat-1 fibroblasts contain a number of trans-acting factors that interact with the positive and negative cis-acting regulatory elements of the SG-PG gene. Furthermore, some of these trans-acting factors appear to be different for the two cell types. These studies on cell types that do and do not express the SG-PG gene indicate that transcription of this proteoglycan peptide core gene is regulated constitutively by both positive and negative cis-acting elements located 5' of an atypical promoter.
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PMID:Negative and positive cis-acting elements in the promoter of the mouse gene that encodes the serine/glycine-rich peptide core of secretory granule proteoglycans. 173 Jun 21

Proteoglycans were extracted from nuclease-digested sonicates of 10(9) rat basophilic leukemia (RBL-1) cells by the addition of 0.1% Zwittergent 3-12 and 4 M guanidine hydrochloride and were purified by sequential CsCl density gradient ultracentrifugation, DE52 ion exchange chromatography, and Sepharose CL-6B gel filtration chromatography under dissociative conditions. Between 0.3 and 0.8 mg of purified proteoglycan was obtained from approximately 1 g initial dry weight of cells with a purification of 200-800-fold. The purified proteoglycans had a hydrodynamic size range of Mr 100,000-150,000 and were resistant to degradation by a molar excess of trypsin, alpha-chymotrypsin, Pronase, papain, chymopapain, collagenase, and elastase. Amino acid analysis of the peptide core revealed a preponderance of Gly (35.4%), Ser (22.5%), and Ala (9.5%). Approximately 70% of the glycosaminoglycan side chains of RBL-1 proteoglycans were digested by chondroitinase ABC and 27% were hydrolyzed by treatment with nitrous acid. Sephadex G-200 chromatography of glycosaminoglycans liberated from the intact molecule by beta-elimination demonstrated that both the nitrous acid-resistant (chondroitin sulfate) and the chondroitinase ABC-resistant (heparin/heparan sulfate) glycosaminoglycans were of approximately Mr 12,000. Analysis of the chondroitin sulfate disaccharides in different preparations by amino-cyano high performance liquid chromatography revealed that 9-29% were the unusual disulfated disaccharide chondroitin sulfate di-B (IdUA-2-SO4----GalNAc-4-SO4); the remainder were the monosulfated disaccharide GlcUA----GalNAc-4-SO4. Subpopulations of proteoglycans in one preparation were separated by anion exchange high performance liquid chromatography and were found to contain chondroitin sulfate glycosaminoglycans whose disulfated disaccharides ranged from 9-49%. However, no segregation of subpopulations without both chondroitin sulfate di-B and heparin/heparan sulfate glycosaminoglycans was achieved, suggesting that RBL-1 proteoglycans might be hybrids containing both classes of glycosaminoglycans. Sepharose CL-6B chromatography of RBL-1 proteoglycans digested with chondroitinase ABC revealed that less than 7% of the molecules in the digest chromatographed with the hydrodynamic size of undigested proteoglycans, suggesting that at most 7% of the proteoglycans lack chondroitin sulfate glycosaminoglycans.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Purification and characterization of protease-resistant secretory granule proteoglycans containing chondroitin sulfate di-B and heparin-like glycosaminoglycans from rat basophilic leukemia cells. 241 30

A cDNA that encodes a mouse secretory granule proteoglycan peptide core was isolated from a cDNA library prepared from nontransformed mouse bone marrow-derived mast cells (BMMC) using as a probe a 280-base-pair fragment of a rat cDNA that encodes the proteoglycan peptide core of rat basophilic leukemia (RBL)-1 cells. Based on the consensus nucleotide sequence and deduced amino acid sequence of the cDNA, the mouse BMMC proteoglycan peptide core is 16.7 kDa and contains a 21-amino acid glycosaminoglycan attachment region consisting of alternating serine and glycine residues. When the predicted amino acid sequence of the mouse BMMC proteoglycan peptide core was compared with the predicted amino acid sequences of the homologous molecules expressed in RBL-1 cells and in human promyelocytic leukemia HL-60 cells, the mouse-derived sequence was more closely homologous to the rat sequence than the human sequence except for the length of the serine-glycine repeat region. The N terminus was found to be a highly conserved region of the molecule in the three species, suggesting that this region is important for the structure, function, and/or metabolism of this family of proteoglycans. Nucleotide sequences within the 5' and 3' untranslated regions of the mouse, rat, and human proteoglycan cDNA were conserved. That similar sequences were also present in the corresponding regions of a cDNA that encodes a rat mast cell protease suggests that particular nucleotide sequences may be important for regulation of expression of those proteins that are destined to reside in secretory granules.
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PMID:Molecular cloning of a cDNA that encodes the peptide core of a mouse mast cell secretory granule proteoglycan and comparison with the analogous rat and human cDNA. 272 51

A cDNA that encodes the peptide core of the secretory granule proteoglycan of the human promyelocytic leukemic cell line, HL-60, has been isolated and analyzed. When human genomic DNA was digested and probed under conditions of low stringency with a rat cDNA that encodes a Mr = 18,600 serine/glycine-rich proteoglycan peptide core in L2 yolk sac tumor cells (Bourdon, M. A., Oldberg, A., Pierschbacher, M., and Ruoslahti, E. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 1321-1325) and basophilic leukemia-1 cells (Avraham, S., Stevens, R. L., Gartner, M. C., Austen, K. F., Lalley, P. A., and Weis, J. H. (1988) J. Biol. Chem. 263, 7292-7296), a number of DNA fragments were identified. A HL-60 cell-derived cDNA library was therefore screened under conditions of low stringency with the rat probe to identify and isolate a human homologue of this rat proteoglycan peptide core. Analysis of the resulting human cDNA clones indicated that the proteoglycan peptide core that is expressed in HL-60 cells is Mr = 17,600 and contains an 18-amino acid glycosaminoglycan attachment region that consists primarily of alternating serin and glycine. Northern blot analysis of total RNA probed with the human cDNA revealed that the major message for this proteoglycan peptide core in HL-60 cells is approximately 1.3 kilobase pairs in size. When a Southern blot of digested human genomic DNA was probed with the human cDNA, three bands of approximately 6, 9, and 12 kilobase pairs were detected. However, when the Southern blot was probed with the XmnI----3' fragment of this human cDNA, one prominent band was detected, indicating that a single gene encodes this protein in the human. Analysis of the DNA from human/mouse and human/hamster somatic cell hybrids probed with the human cDNA demonstrated that the gene that encodes this molecule resides on human chromosome 10. Because the proteoglycans that are present in the secretory granules of different types of rat and mouse mast cells possess small peptide cores that are rich in serine and glycine, we propose that this HL-60 cell-3 derived cDNA encodes the peptide core of the proteoglycan that is expressed in the secretory granules of this human promyelocytic cell.
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PMID:Isolation and characterization of a cDNA that encodes the peptide core of the secretory granule proteoglycan of human promyelocytic leukemia HL-60 cells. 283 70

It has been previously shown that a single gene is used to encode the peptide core of the extracellular proteoglycan of rat L2 yolk sac tumor cells and the intracellular proteoglycan of rat basophilic leukemia (RBL)-1 cells. In order to determine if the predicted amino acid sequences of these proteoglycans are identical as well as to isolate a full length cDNA encoding a rat secretory granule proteoglycan, a cDNA library was prepared from RBL-1 cells and screened with the 165-base pair 5'----XmnI fragment of pPG-1, a partial cDNA which encodes the rat L2 cell proteoglycan peptide core. Based on the consensus nucleotide sequence of two full length RBL-1 cell-derived cDNAs, the 5' untranslated region of the mRNA that is expressed in RBL-1 cells is shorter than that expressed in the rat L2 cells although the coding regions of the mRNAs from the two cell types are identical. These findings indicate that the targeting of proteoglycans to an intracellular or extracellular compartment is a cell-specific event which is independent of the translated peptide core. Since the RBL-1 cell and the rat L2 cell proteoglycans have different types of glycosaminoglycans bound to them, it can also be concluded that the selection of the type of glycosaminoglycan that will be synthesized onto a peptide core is a cell-specific event which is not exclusively dependent on the translated peptide core. When the predicted amino acid sequence of the RBL-1 cell proteoglycan peptide core was compared to the predicted sequence of the homologous human molecule from HL-60 cells, 48% of the amino acids were identical. The N terminus was the most highly conserved area of the molecule. This region of the peptide core, which precedes the serine-glycine repeat region, is likely to be of critical importance for the biosynthesis and/or function of these proteoglycans. Analysis of 10 different mouse/hamster somatic cell hybrid lines with a SspI----3' fragment of the rat L2 cell cDNA revealed that, as in the human, the gene that encodes the mouse analogue of this peptide core resides on chromosome 10.
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PMID:Isolation of a cDNA that encodes the peptide core of the secretory granule proteoglycan of rat basophilic leukemia-1 cells and assessment of its homology to the human analogue. 336 80

Secretory granules of the rat basophilic leukemia (RBL-1) cell, a chemically generated tumor cell line maintained in tissue culture, were shown to stain with alcian blue but not with safranin counterstain and to have sparse, small, electron-dense granules. A Mr 25,000 protein was the major [3H]diisopropyl fluorophosphate-binding protein in extracts of RBL-1 cells. Double-immunodiffusion analysis of extracts revealed immunoreactivity for rat mast cell protease (RMCP)-II, a Mr 25,000 neutral protease present in the secretory granules of rat mucosal mast cells and cultured rat bone marrow-derived mast cells, but no immunoreactivity for RMCP-I, the predominant neutral protease of rat connective tissue mast cells. By radial immunodiffusion, there was 66.8 ng of RMCP-II per 10(6) cells. Whereas rat connective tissue mast cells stain with alcian blue and safranin and contain heparin proteoglycan, rat mucosal and rat bone marrow-derived mast cells stain with alcian blue only and contain a non-heparin proteoglycan and lesser amounts of histamine. Proliferation of rat mucosal mast cells in vivo and rat bone marrow-derived mast cells in vitro requires T-cell factors, whereas no comparable requirement has been observed for connective tissue mast cells. The transformed RBL-1 tumor cells, whose growth is independent of factors other than those present in standard tissue culture medium, has previously been shown to contain predominantly chondroitin sulfate di-B proteoglycans and low amounts of histamine. The similar histology and secretory granule biochemistry of the rat mucosal mast cells, rat culture-derived mast cell, and RBL-1 cell suggest that they comprise a single mast cell subclass distinct from the rat connective tissue mast cell.
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PMID:Homology of the rat basophilic leukemia cell and the rat mucosal mast cell. 392 82

Some lines of colon cancer cells are forced to undergo differentiation by 12-O-tetradecanoylphorbol-13-acetate (TPA). The increases in activities of both protein tyrosine phosphatase (PTP) and protein tyrosine kinase (PTK) have been reported to be associated with the TPA-induced differentiation of HL-60 leukemia cells. In the present study, a 2-fold increase in PTP activity was observed in SW620 human colon cancer cells after 30 min of TPA treatment; a maximal level (4- to 5-fold) was reached at 60 min and continued for more than 6 hr. In addition, two TPA-induced differentiated characteristics, morphological alteration and release of cellular surface proteoglycan, were effectively blocked by PTP inhibitors, such as sodium orthovanadate (50 microM), zinc chloride (100 microM), and iodoacetate (250 microM), but not by the protein serine/threonine phosphatase inhibitor okadaic acid (20 nM). On the other hand, although TPA induced a transient slight increase in PTK activity (1.4-fold) at 60 min, four PTK inhibitors (genistein, herbimycin A, tyrphostin-23 and quercetin) had different effects on the TPA-induced release of cell surface proteoglycan. Genistein (60 microM) potentiated this process, but in contrast, quercetin (45 microM) could partially inhibit the TPA effect. Taken together, these observations suggest that both PTP and PTK activities were increased in SW620 cells in response to TPA; however, the activation of PTP seems to be preferentially required for the TPA-induced differentiation of SW620 human colon cancer cells.
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PMID:Preferential requirement for protein tyrosine phosphatase activity in the 12-O-tetradecanoylphorbol-13-acetate-induced differentiation of human colon cancer cells. 748 37

This study has determined the effects of phorbol-12-myristate-13-acetate (PMA) and dimethylsulfoxide (DMSO) on mRNA levels for the serglycin proteoglycan core protein in human erythroleukemia (HEL) cells. We have compared these changes to those for mRNA for other proteins which are known to be synthesized by HEL cells and megakaryocytes and are known to be localized to alpha granules within platelets. PMA caused a large increase in mRNA for serglycin within two hours of treatment of the cells, and the increase persisted for at least 72 hours. DMSO did not cause a significant change in mRNA levels. mRNA for platelet factor 4, transforming growth factor-beta, and P-Selectin (PADGEM, GMP-140) were also increased by PMA treatment. The mRNA for platelet factor 4 was substantially reduced in the presence of DMSO. The increase of mRNA for serglycin induced by PMA was consistent with our previous observation that synthesis of proteoglycans from [35S]sulfate was greatly stimulated by PMA in HEL cells. The data suggest that up-regulation of synthesis of proteoglycans is induced by PMA in cells which have the capacity to differentiate along the megakaryocytic lineage, as opposed to cell lines such as HL-60 in which proteoglycan synthesis is reduced in the presence of this differentiation-inducing agent.
Leukemia 1993 Dec
PMID:Expression of mRNA for serglycin core protein and other platelet alpha granule proteins is increased in human erythroleukemia cells by phorbol myristate acetate. 750 70

Leukaemia Inhibitory Factor (LIF) has been implicated in connective tissue damage in arthritis. We have previously shown that LIF stimulates proteoglycan release in pig cartilage explants. The aim of this study was to determine whether LIF modulates proteoglycan synthesis in vitro. The methods used were as follows: slices of pig and goat articular cartilage were incubated overnight in Dulbecco's modification of Eagles medium (DMEM), supplemented with 5% foetal calf serum (FCS) and then cultured for 48 h without FCS and either no cytokines (negative control) or LIF. During the final 6 h the tissue was cultured in sulphate free DMEM containing 35SO4. The radioactivity in the medium and tissue was determined in cetylpyridinium chloride precipitates. Biosynthetic activity was expressed as DPM per mg wet weight of cartilage. Dose-dependent suppression of proteoglycan synthesis was observed with murine and human recombinant LIF in pig and goat cartilage. The degree of inhibition was similar to the maximal suppression observed with IL-1 alpha, but was not IL-1 dependent. In conclusion, LIF is a potent inhibitor of proteoglycan synthesis in cultured pig and goat articular cartilage.
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PMID:Leukaemia inhibitory factor (LIF) suppresses proteoglycan synthesis in porcine and caprine cartilage explants. 778 32

We have analysed the mechanism of PMA-induced adhesion of the MDS human leukemia cell line. Affinity to various matrix ligands indicated that PMA induced fibronectin adhesion of MDS cells. This interaction could not be inhibited by RGDS-peptide, therefore it was most probably not mediated by integrins. Rather, both the basal and PMA-induced fibronectin adhesion of MDS cells could be inhibited by heparin and much less efficiently by chondroitin sulphate, suggesting that glycosaminoglycans of proteoglycans may be responsible for the change in adhesive phenotype. PMA stimulation of MDS cells induced a significant increase in proteoglycan biosynthesis. Studies on the glycosaminoglycan pattern of the proteoglycans showed that PMA treatment initiated a shift in glycanation of the MDS-proteoglycans from the predominant chondroitin sulphate-proteoglycans in control cells to a predominant heparan sulphateproteoglycans in adherent cells. These data indicate that protein kinase C, the main target of PMA, may have a profound role in the regulation of glycanation pattern of proteoglycans. Furthermore, such alterations in the cellular proteoglycans may significantly affect the matrix adhesion potential of hematopoietic cells.
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PMID:PMA induces shift from chondroitin to heparan sulphate on proteoglycans correlating with fibronectin adhesion of MDS human leukemia cells. 807 77


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