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)

Chromosome instability is considered to be a probable candidate for a genetic predisposition to cancer. In order to confirm association of heritable fragile sites with cancer, an epidemiologic survey study was conducted which compared their incidence between patients of leukemia and allied diseases, and healthy subjects. The total incidence was 3.2% and 6.0% in patients and controls, which seemed to indicate that the carrier state of a fragile site is not a risk factor for cancer development. However the cases detected in the study were individually quite interesting: One was a coincident case of fra (16) (q22) and inversion of chromosome 16, and another was a coincidence of homozygous fra (17) (p12) and familial clustering of cancers. Chromosome instability, including the fragile sites, should be paid further attentions with respect to its role in the etiology of cancer.
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PMID:[Chromosome instability and cancer]. 347 32

Cerulenin, an inhibitor of de novo fatty acid (and cholesterol) biosynthesis, has been shown to significantly decrease (greater than 75%) the amount of Moloney murine leukemia virus (MMuLV) released into the culture medium of chronically infected mouse fibroblasts (I. Katoh, Y. Yoshinaka, and R.B. Luftig, 1986, Virus Res., in press). In order to clarify the mechanism by which this decrease in virus production occurs, we analyzed the kinetics of gag and env coded protein synthesis in M-MuLV infected, cerulenin-treated cells by immunoprecipitation with monospecific antisera to p30, p12, p10, gp70, and p15(E). We found that in pulse (15 min-2 hr)-chase (0-4 hr) experiments the cleavage of not only Pr65gag to p30 and other gag coded proteins but Pr80env to gp70 and Pr15(E) as well, was greatly reduced by cerulenin treatment. Further, since the total amount of label in the Pr65gag and Pr80env bands remained about the same or was slightly decreased in 2-hr pulsed, cerulenin-treated cells, this suggests that cerulenin decreases virus production, in part, by inhibiting the cleavage of both precursor gag and env coded polyproteins during virus assembly and budding at the cell membrane. We also observed that at longer chase periods (4 hr), the effect of cerulenin could be partially overriden in that minor amounts of cleaved gag and env coded polyproteins were produced and assembled into virion particles. However, these particles contained abnormally large amounts of the uncleaved precursor Pr65gag, suggesting that maturation was incomplete. The above results suggest two independent, but not exclusive, possible mechanisms of cerulenin action to block M-MuLV production, viz. cerulenin decreases the pool of fatty acids, thereby inhibiting fatty acid acylation of Pr65gag, as well as Pr80env, and thus preventing the interaction between gag (the p15 antigenic determinant on Pr65gag) and env [the p15(E) antigenic determinant of Pr15(E)] coded gene products at the cell membrane needed for efficient virus assembly (M. Satake and R. B. Luftig, 1983, Virology 124, 259-273), and cerulenin inhibits one or more proteolytic enzymes responsible for the cleavage of Pr65gag and Pr80env.
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PMID:Inhibition of cleavage of Moloney murine leukemia virus gag and env coded precursor polyproteins by cerulenin. 348 14

We have purified from Moloney murine leukemia virus (Mo-MuLV) a protease that has the capacity of accurately cleaving the polyprotein precursor Pr65gag into the mature viral structural proteins. Both the NH2- and COOH-terminal amino acid sequences have been determined and aligned with the amino acid sequence deduced from the DNA sequence of Mo-MuLV by other workers. The results show that: (i) the protease is located at the 5' end of the pol gene, and the first four amino acids are overlapped with the 3' end of the gag gene; (ii) the fifth amino acid residue is glutamine, which is inserted by suppression of the UAG termination codon at the gag-pol junction; and (iii) the protease is composed of 125 amino acids with calculated Mr = 13,315, and the COOH terminus of the protease is adjacent to the NH2 terminus of reverse transcriptase. The map order of the gag-pol gene is proposed to be 5'-p15-p12-p30-p10-protease-reverse transcriptase-endonuclease-3'.
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PMID:Murine leukemia virus protease is encoded by the gag-pol gene and is synthesized through suppression of an amber termination codon. 388 15

Two low-molecular-weight type-specific virion polypeptides from the Kirsten strain of Murine leukemia virus, polypeptides p10 and p12, are immunologically related by radioimmunoassay competition techniques.
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PMID:Immunological cross-reactions between two low-molecular-weight polypeptides from a murine type C virus. 436 92

Monoclonal antibodies to the p15 and p12 gag proteins were used to detect the P120gag-abl transforming protein of Abelson murine leukemia virus in nonproductively transformed normal rat kidney fibroblast cells. The results demonstrate that, in addition to the prominent plasma membrane location, P120gag-abl was associated with points of adhesion between the cell and the substratum. The localization of P120gag-abl was qualitatively similar to that reported for pp60src in the same normal rat kidney fibroblast cells and suggests that these transforming proteins may share some common transformation features.
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PMID:Detection of the v-abl gene product at cell-substratum contact sites in Abelson murine leukemia virus-transformed fibroblasts. 608 63

Gazdar-murine sarcoma virus (Gz-MSV) particles, obtained from tissue culture fluids of chronically infected HTG-2 hamster cells are immature in morphology and contain uncleaved Pr65gag as the predominant protein (greater than 95% Coomassie blue stain) (A. Pinter and E. deHarven, 1979, Virology 99, 103-110; Y. Yoshinaka and R. B. Luftig, 1982, Virology 118, 380-388). When Gz-MSV particles are disrupted in 1% sodium dodecyl sulfate (SDS) and then analyzed by SDS-polyacrylamide gel electrophoresis (PAGE) in the absence of reducing agents, such as beta-mercaptoethanol (beta-MSH) almost half of the Pr65gag Coomassie blue-stained band is detected as a band at a Mr of 130K. Electrophoretic blotting studies with monospecific antisera against MuLV p30, p15, p12, and p10 showed that the 130K band cross-reacted with all four antigens suggesting that it was a dimer of Pr65gag. Two-dimensional (2D) SDS-PAGE where the first dimension was run under nonreducing conditions and the second with beta-MSH, supported the contention that the 130K band was a dimeric complex of Pr65gag. One also saw minor amounts of a 260K and higher polymeric forms of Pr65gag on the SDS gels, suggesting that polymeric forms may exist as well. When 32P-labeled Gz-MSV particles obtained by in vivo labeling of infected HTG-2 cells with [32P]PPi were electrophoresed on SDS-PAGE, only 10% of the 32P label was detected at the 130K position. In contrast, 30% of the Coomassie blue-stained Pr65gag material was found at 130K on the 2D gels. This suggests that unphosphorylated Pr65gag is more likely to participate in dimer formation than phosphorylated Pr65gag. Pr65gag of Moloney murine leukemia virus (M-MuLV), which is present as a minor (5% of stain) protein band on SDS-PAGE also showed 130K dimers. Further, in beta-MSH-deficient SDS preparations of Gz-MSV, electrophoresed after trypsin treatment, a 32K band that stained with p15, but not p10, p12, nor p30, antisera was observed. If beta-MSH was added, this band was no longer present. Thus Pr65gag dimerization in immature MuLV particles appears to at least involve the p15 region of the polyprotein. Since p15 is an extremely hydrophobic protein, formation of Pr65gag dimers may occur when virion precursor proteins are brought to the cell membrane during virus assembly.
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PMID:Murine retrovirus Pr65gag forms a 130K dimer in the absence of disulfide reducing agents. 608 46

An approach toward elucidation of the mechanisms of action of mammalian leukemia viruses has been made by the generation in tissue culture of recombinant viruses between a potent murine leukemia virus (MuLV), Rauscher-MuLV, and an endogenous xenotropic mouse type-C virus, BALB:virus-2, without known malignant potential. Using a double selection system devised to select against the temperature-sensitive (ts) lesion associated with a mutant of Rauscher-MuLV and the xenotropic host range of BALB:virus-2, recombinant viruses were obtained at frequencies ranging from 0.01 to 0.1%. Recombinant viruses were identified on the basis of the type specific antigenic determinants in the translational products of gag (p15, p12, p30, and p10 proteins), pol (reverse transcriptase), and env (gp70 glycoprotein) genes. By this approach, the partial genetic maps of a large number of recombinants were obtained. The fact that p10 of Rauscher-MuLV ts 25, the mutant utilized, was the only protein uniformly lacking in recombinant viruses, localized the lesion inhibiting gag precursor cleavage in this mutant at the carboxy terminus of its gag gene. The recombinant viruses demonstrated two host range phenotypes as defined by Fv-1 host cell restriction. In each case, NB-tropic recombinants possessed the p30 of BALB:virus-2 p30. Thus, it was possible to assign the site of Fv-1 action at, or closely linked, to the viral p30. The target within the viral genome of a second host restriction was also mapped. A serum factor, previously shown to specifically inactivate xenotropic virus infectivity, was demonstrated to exert its action on the viral env gene product. The system described here allows the generation of specific recombinant genotypes that should be useful in defining those regions of the viral genome involved in leukemogenesis.
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PMID:Viral genes involved in leukemogenesis. I. Generation of recombinants between oncogenic and nononcogenic mouse type-C viruses in tissue culture. 615 14

Gel filtration chromatography of disrupted bovine leukaemia virus (BLV) resulted in the isolation of the 25000 mol. wt. major internal protein (p25), two previously uncharacterized proteins of mol. wt 65000 (p65) and 12000 (p12), and a mixture of p12 and a protein of mol. wt. 15000 (p15). The p65 protein does not bind to concanavalin A and its antigenicity is ether resistant. Therefore, this polypeptide is different from the previously described glycoprotein associated with BLV. Radioimmunoprecipitation and competitive radioimmunoassays indicated that the p65 protein shares antigenic determinants with the p25, p15 and p12 proteins, respectively. Furthermore, tryptic peptide mapping demonstrated that p65 contains p25, p15, p12 and a BLV protein of mol. wt. 10000 (p10). These results are consistent with the view that p65 is the precursor of gag gene-derived core proteins of BLV.
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PMID:Detection of a precursor-like protein of bovine leukaemia virus structural polypeptides in purified virions. 615 29

Fresh human sera neutralize Friend leukaemia virus (FLV). The activity is abolished by heating (56 degrees C for 30 min), hydrazine and EDTA treatment, suggesting the involvement of complement. Human sera also contain antibody which specifically reacts with FLV. Following incubation with human whole serum, IgG and F(ab')2 fragments, FLV acquire the ability to bind anti-human Ig sera, as shown in neutralization and radioimmunoprecipitation assay. The same is true for FLV-infected cells but not for uninfected control cells, as assessed by immunofluorescence. The binding of antibody to FLV-infected cells is prevented by pre-treating the cells with antisera to FLV and FLV-gp71, and is completed by FLV, FLV-gp71 and, to a lesser extent, by FLV-p12 and p30.
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PMID:Immunoglobulins in human serum reactive with murine Friend leukaemia virus. 615 29

Moloney leukemia virus (MoLV) induces lymphomas in BALB/c mice which either involve an immature thymic T-cell subpopulation or a splenic mature T-cell subpopulation. To investigate further the possible virological and immunological differences in these lymphomas, several lymphoma cell lines were derived. Although the majority of these cell lines expressed only the parental MoLV, one lymphoma cell line (5F4) was found which expressed only a defective virus. 5F4 virions lacked detectable reverse transcriptase activity and by immunoprecipitation lacked a serologically detectable reverse transcriptase. The lack of reverse transcriptase did not appear to be due to a deletion in the viral genome. Intracellularly 5F4 cells synthesized normal gag gene precursors but had little, if any, detectable Pr180gag-pol or an altered precursor. These results suggest that the defect of the 5F4 virus is associated with the inability to translate the appropriate precursor for reverse transcriptase. The possible origin of the detective 5F4 virus was also examined by competition radioimmunoassays. These results demonstrate that the type-specific proteins, gp71 and p12, are serologically identical to those of the endogenous ecotropic virus and distinct from the MoLV proteins. Competition assays of 5F4 cell extracts further demonstrated the lack of any detectable MoLV type-specific proteins, although the tumor was presumably induced by MoLV. The significance of these observations to leukemogenesis is discussed.
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PMID:Characterization of a unique defective type C virus associated with a Moloney leukemia virus-induced splenic T-cell lymphoma cell line. 615 81


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