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)

Low molecular weight chromatin peptides exert a dose-dependent inhibition of Dimethylsulfoxide (DMSO)-induced erythroid differentiation of murine Friend Leukemia Cells (FLC). This effect correlates with the degree of purification of the peptide fractions. Crot analysis of globin mRNA amounts in DMSO-treated FLC given the peptides showed a 4-5-fold decrease of messenger RNA in the cytoplasma with no nuclear storage of globin transcripts. Spectrin accumulation in "induced" FLC is inhibited as well. The effects of the peptides on erythroid markers are reversible upon removal of the compounds. They also appear to be specific for induced gene expression as (1) no effects are observed on cell growth and RNA synthesis in normal non-differentiating cell lines; and (2) no changes have been detected with regard to the expression of integrated viral genes coding for continuous shedding of viral particles.
Mol Biol Rep 1979 Dec 31
PMID:Effects of a chromatin low molecular weight peptidic fraction on differentiation markers and virus production in Friend leukemia cells. 9 93

Tumor cell resistance due to enhanced efflux of drugs with diverse structures and/or mechanisms of action is termed multidrug resistance (MDR), and modulation of the MDR phenotype by calcium blockers or calmodulin inhibitors is suggested to involve P-glycoprotein. In drug-sensitive (S) and 5-fold doxorubicin (DOX)-resistant (R0) L1210 mouse leukemia cells, no obvious differences in mdr mRNA or P-glycoprotein expression or alterations in cellular uptake, retention, or cytotoxicity of vincristine (VCR) were observed. However, in the 10-fold (R1) and 40-fold (R2) DOX-resistant sublines, expression of P-glycoprotein was correlated with the level of resistance (R2 greater than R1). An RNase protection assay revealed that elevated levels of mdr1 and mdr2 mRNA were detected in R1 and R2 cells, with an additional increase in mdr3 mRNA in the R2 subline. Further, in the R1 and R2 sublines, no VCR dose-dependent cytotoxicity was apparent, and cell kill of greater than 40% was not achievable following a 3-hr drug exposure. Cellular uptake and retention of VCR were 2- to 4-fold lower in the R1 and R2 sublines, compared with similarly treated S or R0 cells. Potentiation of VCR cytotoxicity by a noncytotoxic concentration of 5 microM trifluoperazine (TFP) was greater than 2-fold in S and R0 cells and less than 1.3-fold in the R1 and R2 sublines. Modulation of VCR uptake by 5 microM TFP in the S and R0 cells was 2-fold and it was 4- to 7-fold in the R1 and R2 sublines. The presence of 5 microM TFP, by competing for efflux, enhanced VCR retention 1.5-fold in S and R0 cells and 2- to 4-fold in the R1 and R2 sublines. In contrast to these results with VCR, dose-dependent cytotoxicity of DOX was apparent in all the resistant sublines, and modulation of DOX cytotoxicity by 5 microM TFP was dependent on the level of resistance. Cellular accumulation of DOX was 20 and 50% lower in the R1 and R2 sublines, respectively, compared with similarly treated S or R0 cells. Marked increases (greater than 1.5-fold) in cellular accumulation of DOX by TFP were apparent only in the R2 subline. Results suggest that a relationship between overexpression of P-glycoprotein isoforms and their role in affecting cellular drug levels and consequent cytotoxicity in MDR L1210 cells determines resistance to VCR but not DOX.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Pharmacol 1991 Jan
PMID:Relationship between expression of P-glycoprotein and efficacy of trifluoperazine in multidrug-resistant cells. 167 Sep 62

The effect of cyanomorpholinyldoxorubicin, morpholinyldoxorubicin, doxorubicin, and Actinomycin D were studied on purified mouse leukemia (L1210) DNA topoisomerases I and II. DNA unwinding and cross-linking were also studied. It was found that 1) morpholinyldoxorubicin, cyanomorpholinyldoxorubicin, and Actinomycin D (but not doxorubicin) stimulated DNA topoisomerase I-induced cleavage at specific DNA sites; 2) only doxorubicin and Actinomycin D stimulated DNA cleavage by DNA topoisomerase II; 3) at higher drug concentrations, DNA intercalators suppressed enzyme-mediated DNA cleavage induced by DNA topoisomerase I, as well as topoisomerase II; 4) only cyanomorpholinyldoxorubicin produced DNA-DNA cross-links; no DNA unwinding could be observed; and 5) DNA intercalation (unwinding) potency of morpholinyldoxorubicin was about 2-fold less than that of doxorubicin. The data indicate that some DNA intercalators are not only inhibitors of DNA topoisomerase II but act also on DNA topoisomerase I. The stabilization of cleavage intermediates by intercalators may have a common mechanism for DNA topoisomerase I and DNA topoisomerase II.
Mol Pharmacol 1990 Jul
PMID:Effects of morpholinyl doxorubicins, doxorubicin, and actinomycin D on mammalian DNA topoisomerases I and II. 216 30

Transmembrane equilibration of 2',3'-dideoxyadenosine (ddAdo) was measured by rapid kinetic techniques in deoxycoformycintreated P388 and L1210 mouse leukemia cells and human erythrocytes, at 25 degrees. It was only about 10% as rapid as that of other purine nucleosides that are known substrates for the nucleoside transporters of these cells. ddAdo entry was nonsaturable up to a concentration of 1 mM and was not inhibited by other nucleosides or two nucleoside transport inhibitors, dipyridamole and nitrobenzylthioinosine. Thus, ddAdo permeation was mainly nonmediated. It was relatively rapid because of the high lipid solubility of ddAdo. ddAdo entered the cells at least 100 times more rapidly than dideoxycytidine but less rapidly than trideoxythymidine, with an even greater lipophilicity than ddAdo. ddAdo was not phosphorylated in human erythrocytes, but there was some phosphorylation in deoxycoformycin-treated P388 and L1210 cells. In situ conversion of 10 microM ddAdo to ddATP, however, was slow and ceased after 5-10 min at 25 degrees or 37 degrees. Cessation of net uptake was not due to turnover of dideoxy-ATP or deamination of dideoxy-AMP. The results suggest that ddAdo salvage in the absence of deamination is limited by feedback inhibition of its phosphorylation, perhaps by deoxycytidine kinase. Permeation into the cells was not rate limiting to ddAdo salvage. In P388 and L1210 cells that had not been treated with deoxycoformycin, ddAdo was salvaged at least 100 times more efficiently than in deoxycoformycin-treated cells and converted to nucleoside triphosphates, but the end-products and pathways of salvage have not been resolved entirely. Salvage of ddAdo required deamination but was not primarily via dideoxyinosine----hypoxanthine----IMP, as is the case for 2'-deoxyadenosine salvage, because [3H]ddAdo salvage was only little inhibited by unlabeled hypoxanthine, whereas it was strongly inhibited by 2'-deoxyadenosine, adenosine, and adenine.
Mol Pharmacol 1989 Jul
PMID:Permeation and salvage of dideoxyadenosine in mammalian cells. 278 72

L1210 mouse leukemia cells exhibit two distinct types of nucleoside transport activity that have similar kinetic properties and substrate specificity, but differ markedly in their sensitivity to the inhibitor nitrobenzylthioinosine (NBMPR) (Belt, J. A. (1983) Mol. Pharmacol. 24, 479-484). It is not known whether these two transport activities are mediated by a single protein or by separate and distinct nucleoside transport proteins. We have isolated a mutant from the L1210 cell line that has lost the NBMPR-insensitive component of nucleoside transport, but retains NBMPR-sensitive transport. In the parental cell line 20-40% of the nucleoside transport activity is insensitive to 1 microM NBMPR. In the mutant, however, uridine and thymidine transport are almost completely inhibited by NBMPR. Consistent with the loss of NBMPR-insensitive transport, the mutant cells can be protected from the toxic effects of several nucleoside analogs by NBMPR. In contrast, the toxicity of the same analogs in the wild type cells is not significantly affected by NBMPR, presumably due to uptake of the nucleosides via the NBMPR-insensitive transporter. On the other hand, NBMPR-sensitive transport in the mutant appears to be unaltered. The mutant is not resistant to cytotoxic nucleosides in the absence of NBMPR and the cells retain the wild type complement of high affinity binding sites for NBMPR. Furthermore, the affinity of the binding site for the inhibitor is similar to that of parental L1210 cells. These results suggest that NBMPR-sensitive and NBMPR-insensitive nucleoside transport in L1210 cells are mediated by genetically distinct proteins. To our knowledge this is the first report of a mutant deficient in NBMPR-insensitive nucleoside transport.
 ...
PMID:Isolation and characterization of a mutant of L1210 murine leukemia deficient in nitrobenzylthioinosine-insensitive nucleoside transport. 297 Oct 45

The library of genes was obtained from erythroleukemic AKR cells (C-1), that were maintained as suspension culture. Thirty four clones that had homology with 60-70S RNA of Rauscher Leukemia virus (RLV) were separated from this library. The restriction mapping was carried out with 14 clones, that contained most extensive proviral sequences. One clone (107) contains proviral sequences that are derived from one of the components of the RLV complex. The other 13 clones contain sequences of endogenous xenotropic viruses. The endogenous retroviral sequences obtained differ in restrictive maps from proviruses of ecotropic and xenotropic infectious endogenous MuLV and, apparently, might be attributed as non-inducible infectious xenotropic MuLV of class III. Some of the cloned retroviral sequences had symmetrical structure, that is typical for integrated proviruses, i. e. these sequences were separated from flanking cellular ones by long terminal repeats. All investigated retroviral sequences are deletion mutants of MuLV proviruses. It was shown that the inner regions of proviruses diverged more than the long terminal repeats. The expression of the main inner MuLV polypeptide (p30) was detected in NIH 3T3 cells, transfected with DNA of some clones.
Mol Biol (Mosk)
PMID:[Molecular cloning of MuLV proviruses integrated into the genome of mouse erythroleukemia cells. I. Characteristics of endogenous proviruses]. 299 91

Many highly homologous genes are present in the murine major histocompatibility complex (MHC) class I gene family. Consequently, it is difficult to distinguish between RNA transcripts of individual class I genes solely on the basis of nucleic acid hybridization analysis using DNA probes over 50 base pairs long. To avoid this problem, I have designed and synthesized a set of oligonucleotide probes capable of detecting transcripts of single class I genes in the MHC of C57BL/10 mice or sets of allelic class I genes at the same genetic locus in MHC disparate mouse strains. Using these probes, it is possible to determine the relative abundance of specific class I gene transcripts in a wide variety of cell and tissue types from inbred or MHC disparate mice. Examples of the use of these probes to detect different class I gene transcripts in cloned murine T cells, T cells transformed with Radiation Leukemia Virus, chemically induced thymoma cell lines and embryonic tissues are described. The results of these experiments are discussed in the light of possible roles of class I antigens in tumorigenesis or in early development.
Mol Cell Probes 1987 Sep
PMID:Analysis of major histocompatibility complex class I gene transcription using oligonucleotide probes. 350 10

We have investigated the role of glutathione in determining the macromolecular binding and cytotoxicity of cisplatin (DDP) and melphalan (LPAM) in human ovarian carcinoma cells and DDP-resistant L1210 mouse leukemia cells. Glutathione reacted avidly with DDP in normal saline with a bimolecular rate constant of 16.2 M-1 hr-1. Glutathione had no effect on the rate of hydrolysis of LPAM, consistent with the SN1-like reaction mechanism of LPAM. Glutathione protected calf thymus DNA and bovine serum albumin from DDP platination and LPAM alkylation. Glutathione also protected nuclei isolated from human ovarian carcinoma cells from DDP platination. The importance of intracellular glutathione in determining the cytotoxicity of DDP and LPAM was assessed by depletion of glutathione with buthionine sulfoximine in three cell types. Exposure to 0.5 mM buthionine sulfoximine for 20-28 hr depleted glutathione to levels that were 10-20% of control levels. COLO 316 and 2008 human ovarian carcinoma cells, and ZCR9 mouse leukemia cells were all sensitized to LPAM cytotoxicity by this level of glutathione depletion. The dose modification factors, defined as the IC50 control cells/IC50 depleted cells, were: 2.6 +/- 0.5 for COLO 316 cells, 1.6 +/- 0.1 for 2008 cells, and 2.1 +/- 1.1 for ZCR9 cells. In contrast, glutathione depletion had a minimal effect on DDP cytotoxicity in these cells with dose modification factors of: 1.2 +/- 0.2 for COLO 316 cells, 0.8 +/- 0.3 for 2008 cells, and 1.1 +/- 0.1 for ZCR9 cells. The differential potentiation of DDP and LPAM cytotoxicity by glutathione depletion in these cells, despite the similar protection that glutathione affords macromolecules from drug binding, suggests that there are fundamental differences in the intracellular interaction of these electrophilic drugs with glutathione.
Mol Pharmacol 1986 Dec
PMID:Differential sensitization of human ovarian carcinoma and mouse L1210 cells to cisplatin and melphalan by glutathione depletion. 378 41

We have used chicken anti-mouse immunoglobulin antiserum to precipitate molecules from mouse T-lymphoma cells that had been radioiodinated. We analysed the immunoprecipitates by two-dimensional gel electrophoresis and compared the results with immunoprecipitates generated by other antisera. We found that the molecule precipitated by chicken anti-mouse immunoglobulin from T-lymphoma cells was identical to the mouse leukemia virus envelope glycoprotein (gp 70) produced by the T-lymphoma. Mouse IgM myeloma proteins block precipitation of T-lymphoma molecules by chicken anti-mouse immunoglobulin. We conclude that mouse IgM and gp 70 share antigenic determinants. This may lead to erroneous conclusions about the presence of immunoglobulin on T-cells.
Mol Immunol 1982 Aug
PMID:Murine T-lymphoma 'immunoglobulin' is identical to leukemia virus gp 70. 629 Aug 78

Leukemia results from the accumulation of multiple genetic alterations that disrupt the control mechanisms of normal growth and differentiation. The use of inbred mouse strains that develop leukemia has greatly facilitated the identification of genes that contribute to the neoplastic transformation of hematopoietic cells. BXH-2 mice develop myeloid leukemia as a result of the expression of an ecotropic murine leukemia virus that acts as an insertional mutagen to alter the expression of cellular proto-oncogenes. We report the isolation of a new locus, Meis1, that serves as a site of viral integration in 15% of the tumors arising in BXH-2 mice. Meis1 was mapped to a distinct location on proximal mouse chromosome 11, suggesting that it represents a novel locus. Analysis of somatic cell hybrids segregating human chromosomes allowed localization of MEIS1 to human chromosome 2p23-p12, in a region known to contain translocations found in human leukemias. Northern (RNA) blot analysis demonstrated that a Meis1 probe detected a 3.8-kb mRNA present in all BXH-2 tumors, whereas tumors containing integrations at the Meis1 locus expressed an additional truncated transcript. A Meis1 cDNA clone that encoded a novel member of the homeobox gene family was identified. The homeodomain of Meis1 is most closely related to those of the PBX/exd family of homeobox protein-encoding genes, suggesting that Meis1 functions in a similar fashion by cooperative binding to a distinct subset of HOX proteins. Collectively, these results indicate that altered expression of the homeobox gene Meis1 may be one of the events that lead to tumor formation in BXH-2 mice.
Mol Cell Biol 1995 Oct
PMID:Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice. 756 94


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