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)

Tax1 of human T-cell leukemia virus type 1 (HTLV-1) is a transcriptional activator for viral gene expression and is also a transforming protein through inducing the expression of several cellular genes under the control of mitogenic signals. We identified the CArG boxes as a Tax1-responsive cis-acting element for the cellular immediate early genes c-fos, egr-1, and egr-2. Using a chimeric protein consisting of the CArG-binding factor p67SRF and the heterologous DNA-binding domain of a yeast transcription factor GAL4, we demonstrated that Tax1 activates the transcriptional activity of p67SRF through the GAL4-binding site. The carboxy-terminal half of p67SRF, which lacks domains for DNA-binding, dimerization, and ternary complex formation with p62TCF, was sufficient for the activation by Tax1. Tax1 produced in Escherichia coli bound p67SRF in vitro. The complex formation in vivo was also indicated by the finding that the acidic activation domain of VP16, by fusion to p67SRF, can complement the transcriptional activation function of a mutant Tax1 in trans. Thus, Tax1 activates CArG-mediated transcription without mitogenic signals through interaction with a CArG-binding factor, p67SRF. This must be one of the primary steps by which Tax1 causes aberration in growth control of the infected cells.
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PMID:Interaction of HTLV-1 Tax1 with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes. 142 72

The hst-2 gene was previously identified by its close homology to the hst-1 gene. Cosmid clones containing the hst-2 gene were cloned from a normal human genomic library. Focus-forming activity was observed for the hst-2 cosmids when NIH3T3 transfection assay was performed in a serum-free medium, whereas induction of morphological transformation was difficult to detect in an ordinary serum-supplemented medium. The hst-2 cDNA was cloned from the NIH3T3 transformant. Nucleotide sequence analysis of the cDNA indicates that the hst-2 gene encodes a 198 amino acid transforming protein containing a signal peptide with the characteristics of a heparin-binding growth factor. The coding sequence was almost identical to the published portion of the exon sequence of the FGF-6 gene, indicating that hst-2 is identical to FGF-6. The hst-2 cDNA fragment, when inserted into an expression vector, was able to transform NIH3T3 cells effectively, and the resulting transformant formed a well-vascularized tumor in nude mice, thus suggesting an angiogenic property similar to some other members of the family. RNA blot analysis revealed the expression of the hst-2 gene in human leukemia cell lines with platelet/megakaryocytic differentiation potential.
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PMID:Human hst-2 (FGF-6) oncogene: cDNA cloning and characterization. 154 52

Abelson murine leukemia virus is an acutely transforming replication-defective virus which encodes a transforming protein with tyrosine-specific protein kinase activity. A variety of benzopyranone and benzothiopyranone derivatives have been identified which selectively inhibit the v-abl tyrosine protein kinase with 50% inhibitory concentrations ranging from 1 to 30 microM. The most active derivative inhibited v-abl with a Ki value of 0.9 microM. Active derivatives showed selectivity for the v-abl tyrosine protein kinase relative to the epidermal growth factor receptor tyrosine protein kinase (50% inhibitory concentration greater than 100 microM). Protein kinase C and protein kinase A, two members of the serine/threonine protein kinase family, were not inhibited by benzopyranones or benzothiopyranones (50% inhibitory concentration greater than 100 microM). Kinetically, a representative derivative (compound 2) showed competitivity with respect to ATP and noncompetitive behavior with respect to the exogenous peptide substrate. Autophosphorylation of p120v-abl and recombinant p70v-abl tyrosine protein kinases were also inhibited by benzopyranones and benzothiopyranones in vitro. When tested in Abelson murine leukemia virus-transformed BALB/c cell, active benzopyranone and benzothiopyranone derivatives inhibited tyrosine phosphorylation of cellular proteins by the v-abl tyrosine protein kinase.
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PMID:Benzopyranones and benzothiopyranones: a class of tyrosine protein kinase inhibitors with selectivity for the v-abl kinase. 164 41

Phosphotyrosine proteins of four different tumor cell lines were characterized by monoclonal antibodies exhibiting high affinity binding to phosphotyrosine. For the preparation of the antibody-producing mouse hybridoma cell lines we used a novel kind of immunizing antigen with phosphotyramine conjugated directly to carboxylic groups of carrier proteins. Screening for high affinity binding antibodies was based on their selective reactivity in immunoprecipitation, affinity chromatography and immunofluorescence. By means of affinity chromatography we established a one-step purification of phosphotyrosine proteins yielding substantial quantities of highly pure 170kDa EGF receptor from A431 tumor cells, 210kDa bcr-abl gene product from K562 tumor cells and 120 kDa transforming protein of the Abelson murine leukemia virus from TK tumor cells. Cross-reactivity with phosphoproteins containing no phosphotyrosine was not observed.
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PMID:Highly specific characterization of tyrosine phosphoproteins in tumor cells based on monoclonal antibodies defined by conjugated phosphotyramine. 169 48

Novel antibodies were raised against a synthetic NH2-terminal myristoyl glycine moiety which is characteristic of N-myristoyl-proteins. Antisera raised against N-myristoyl-Gly-hemocyanin reacted with N-myristoyl-Gly-[125I]albumin. The immunoreaction was competed for by albumin conjugated with N-myristoyl-glycine, while underivatized albumin had no effect. Of the [3H]myristate-labeled proteins detected, pp60v-src, which is a transforming protein of Rous sarcoma virus, and p19gag and p17gag, which are core proteins in the human T-cell leukemia virus and the human immunodeficiency virus, were identified as N-myristoylated proteins by the radioimmunoprecipitation analyses with the antibody.
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PMID:Antibodies to an NH2-terminal myristoyl glycine moiety can detect NH2-terminal myristoylated proteins in the retrovirus-infected cells. 254 72

We have developed a one-step purification procedure for proteins containing the N-terminal portion of the gag protein of avian sarcoma and leukemia viruses. In this procedure, a resin with a covalently attached monoclonal antibody to the gag protein p19 is used to bind gag-containing proteins from crude extracts. After washing of the resin, the bound proteins are eluted with 2 M MgCl2. For the transforming protein kinase encoded by Fujinami sarcoma virus p130gag-fps, this procedure gave an enrichment of several thousand-fold, a yield of over 10%, a final purity of over 20%, and no significant loss of protein kinase activity. Similar purifications were obtained with three other gag-containing proteins. The immunoaffinity purification described may be of general utility as a first step in purification of the several other avian retroviral transforming proteins that are synthesized from fusions of an oncogene with the viral gag gene.
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PMID:A simple method for immunoaffinity purification of nondenatured avian sarcoma and leukemia virus gag-containing proteins. 282 89

Avian cellular sequences homologous to the ets domain of the avian leukemia retrovirus, E26, have been characterized, and shown to contain nine discrete regions within a single locus of about 60 kb. The structure of the viral homologous and nonhomologous domains of this chicken ets-1 gene is characterized and seen to define the unique amino acid sequences of the ets protein. We have isolated and sequenced an avian ets-1 cDNA clone obtained from chicken thymus. This cDNA clone contains an open reading frame (ORF) encoding the normal cellular product of 441 amino acids. This product is significantly smaller than that encoded by the v-ets domain of the E26 transforming protein, p135, which contains 491 amino acids. The open reading frame predicted by our sequence data results in a protein calculated to be 50 kDa, which is slightly smaller than that actually observed in chicken cells. The presence of termination codons 5' to this ORF demonstrates that the cDNA characterized contains the entire coding region for the chicken ets gene.
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PMID:A unique amino-terminal sequence predicted for the chicken proto-ets protein. 284 7

A common site of ecotropic murine leukemia virus integration designated Evi-2 (ecotropic viral integration site-2) has been identified in BXH-2 myeloid tumors. As part of experiments to determine whether Evi-2 identified a new proto-oncogene locus involved in myeloid disease, we determined its chromosomal location. We mapped Evi-2 to mouse Chromosome 11 using standard recombinant inbred strain and genetic backcross analysis. We then determined the location of Evi-2 relative to other proto-oncogene and growth factor loci located on Chromosome 11 by interspecific backcross analysis. The loci included in this study were the proto-oncogene loci, Erbb, Erba, and Rel, as well as, Il-3 (interleukin-3), Csfgm (granulocyte-macrophage colony stimulating factor), and Trp53-1 (transforming protein p53). All loci except Erbb had been previously mapped to Chromosome 11 with the use of somatic cell hybrids and consequently their positions on Chromosome 11 were not known. One proto-oncogene, Erbb-2 (analogous to the neu proto-oncogene), and one growth factor locus, Csfg (granulocyte colony-stimulating factor), which had not been mapped in the mouse were also localized on Chromosome 11 using the interspecific backcross mice. Recombination between Evi-2 and all proto-oncogene and growth factor loci was demonstrated, suggesting that Evi-2 may ultimately identify a new proto-oncogene involved in myeloid disease. This study revealed a number of interesting conserved linkage groups common to mouse and man.
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PMID:Localization of Evi-2 to chromosome 11: linkage to other proto-oncogene and growth factor loci using interspecific backcross mice. 285 Nov 24

We previously described a recombinant Moloney murine leukemia virus (Mo-MuLV) carrying the v-src oncogene, Mo-MuLV(src). Mo-MuLV(src) encodes a gag-src fusion protein, transforms cells in culture, and induces fibrosarcomas in vivo. To compare transforming properties of the gag-src fusion protein to pp60src encoded by Rous sarcoma virus, we constructed a new recombinant virus, Mo-MuLV(+ src). Mo-MuLV(+ src) encodes pp60src in the context of Mo-MuLV. Cells transformed by Mo-MuLV(+ src) were round and formed colonies in soft agar, whereas Mo-MuLV(src)-infected cells were fusiform and did not grow in suspension. Thus, the extent of transformation induced by Mo-MuLV(+ src) was greater than that induced by Mo-MuLV(src). Subcutaneous inoculation of either virus into neonatal NIH Swiss mice resulted in fibrosarcomas at the site of injection. Further studies indicated that tumors induced by Mo-MuLV(+ src) grew rapidly but rarely metastasized. In contrast, tumors induced by Mo-MuLV(src) grew somewhat more slowly but metastasized with a high frequency (60%). These viruses may provide a useful model system for tumor metastasis. Another src-containing virus was also studied, MRSV (constructed by Anderson and Scolnick). MRSV also encodes pp60src but in the context of amphotropic MuLV. When injected intravenously into six-week-old mice, MRSV induced splenomegaly and spleen foci but no solid tumors, as reported previously. In contrast, Mo-MuLV(src)-induced fibrosarcomas mostly in the spleen under the same inoculation protocol. These results suggest that the v-src oncogene was the major pathogenic determinant in neonatal mice for all three src-containing viruses; however, variations in the nature of the transforming protein modulated the behavior of the induced tumors. In adult mice, greater differences in pathogenicity were observed.
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PMID:Comparison of three recombinant murine leukemia viruses carrying the v-src oncogene of avian sarcoma virus: differences in in vitro transformation and in vivo pathogenicity. 285 3

The lipid bound to p60src, the transforming protein of Rous sarcoma virus, has been identified by gas and thin-layer chromatography as the 14-carbon saturated fatty acid, myristic acid. The protein can be labeled biosynthetically with either [3H]myristic acid or [3H]palmitic acid. Incorporation of [3H]myristic acid was noticeably greater than incorporation of [3H]palmitic acid. All of the [3H]myristic acid-derived label in p60src was present as myristic acid. In contrast, none of the radioactivity derived from [3H]palmitic acid was recovered as palmitic acid. Instead, all 3H incorporated into p60src from [3H]palmitic acid arose by metabolism to myristic acid. The cellular tyrosine kinase, p60c-src also contains myristic acid. By comparison of the extent of myristylation of p60v-src with that of the Moloney murine leukemia virus structural protein precursor, Pr65gag, we estimate that greater than 80% of the molecules of p60v-src contain one molecule of this fatty acid. Myristylation is a rare form of protein modification. p60v-src contains 10 to 40% of the myristic acid bound to protein in cells transformed by Rous sarcoma virus and is easily identified in total cell lysates when [3H]myristic acid-labeled proteins are separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Comparison of the amount of [3H]myristic acid-labeled p60src in total cell lysates and in immunoprecipitates suggests that immunoprecipitation with rabbit anti-Rous sarcoma virus tumor sera detects ca. 25% of the p60src present in cells.
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PMID:Myristic acid, a rare fatty acid, is the lipid attached to the transforming protein of Rous sarcoma virus and its cellular homolog. 298 63


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