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)

Gardner-Rasheed feline sarcoma virus (GR-FeSV) is an acute transforming retrovirus which encodes a gag-onc polyprotein possessing an associated tyrosine kinase activity. The integrated form of this virus, isolated in the Charon 21A strain of bacteriophage lambda, demonstrated an ability to transform NIH/3T3 cells at high efficiency upon transfection. Foci induced by GR-FeSV DNA contained rescuable sarcoma virus and expressed GR-P70, the major GR-FeSV translational product. The localization of long-terminal repeats within the DNA clone made it possible to establish the length of the GR-FeSV provirus as 4.6 kilobase pairs. The analysis of heteroduplexes formed between lambda feline leukemia virus (FeLV) and lambda GR-FeSV DNAs revealed the presence of a 1,700-base-pair FeLV unrelated segment, designated v-fgr, within the GR-FeSV genome. The size of this region was sufficient to encode a protein of approximately 68,000 daltons and was localized immediately downstream of the FeLV gag gene coding sequences present in GR-FeSV. Thus, it is likely that this 1.7-kilobase-pair stretch encodes the onc moiety of GR-P70. Utilizing probes representing v-fgr, we detected homologous sequences in the DNAs of diverse vertebrate species, implying that v-fgr originated from a well-conserved cellular gene. The number of cellular DNA fragments hybridized by v-fgr-derived probes indicated either that proto-fgr is distributed over a very large region of cellular DNA or represents a family of related genes. By molecular hybridization, v-fgr was not directly related to the onc genes of other known retroviruses having associated tyrosine kinase activity.
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PMID:Molecular cloning of integrated Gardner-Rasheed feline sarcoma virus: genetic structure of its cell-derived sequence differs from that of other tyrosine kinase-coding onc genes. 631 85

The feline oncornavirus-associated cell membrane antigen (FOCMA) on the surface of feline lymphosarcoma (LSA) cells is defined as the target(s) recognized in immunofluorescence (IFA) tests by antibody in sera of cats relatively resistant to development of FeLV (feline leukemia virus) LSA and FeSV (feline sarcoma virus) fibrosarcoma. The specificities of antibodies in cat FOCMA-typing sera and the nature of the LSA antigens recognized were investigated in the present study. FOCMA sera obtained from viremic cats were separable into at least two classes : those which contained antibodies against the envelope glycoprotein (gp70) of subgroup C FeLV and those which did not contain antibodies against any subgroup of FeLV. The first class of sera could be further subdivided into three groups: those whose FOCMA reactivity could be completely absorbed, partially absorbed, or not absorbed by FeLV-C antigens. The second class of sera could be further subdivided into two groups: those whose FOCMA reactivity could be partially absorbed and those whose activity could not be absorbed by FeLV-C. The results indicate that the FOCMA reactivity exhibited by some viremic cat sera can be partially, if not entirely, attributed to antibodies not crossreactive with FeLV virion antigens. A consistent property of all FOCMA sera in this study is the ability to bind to 70-kDa proteins on the surface of LSA cells. Staphylococcus aureus V8 protease partial digest maps of 70-kDa proteins purified from 12 primary feline LSAs (five FeLV positive and seven FeLV negative) all showed 18-, 14-, and 10-kDa fragments. V8 maps of FeLV-C gp70 showed similarly sized fragments while the maps of the RD114, FeLV-A, and FeLV-B gp70s were distinct. However, in a subgroup-specific radioimmunoassay for FeLV-C gp70-related antigens, the LSA 70-kDa proteins were found to be serologically related to, but distinct from, FeLV-C gp70. The results on the antigenic variations among LSA 70-kDa proteins and the antibodies which bind them are entirely consistent with previous studies indicating heterogeneity among FOCMA determinants.
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PMID:The feline oncornavirus-associated cell membrane antigen (FOCMA) is related to, but distinguishable from, FeLV-C gp70. 631 34

The fate of tumors and associated retroviremia was studied in 111 cats infected with the Snyder-Theilen strain of feline sarcoma virus (FeSV). Tumors appeared at the site of inoculation within 7 to 10 days. A retroviremia, due mainly to the associated feline leukemia virus helper virus (FeLV-helper), developed at the same time as tumors. Of the cats, 44 developed progressively growing tumors and therefore had to be killed, and 67 developed tumors that regressed. There was a strong correlation between the persistence of the accompanying retroviremia and the growth of the tumors. The 44 cats with progressively growing fibrosarcomas remained retroviremic until death. Conversely, 53 of the 67 cats with solitary, regressing tumors were only transiently retroviremic. Tumor regression in these cats paralleled the disappearance of retrovirus from the blood. The fate of tumors and retroviremia was not always the same, however. Twelve cats remained persistently retroviremic after all signs of gross tumors disappeared. Two other kittens became nonviremic within 20 days after inoculation, yet tumors continued to grow and even metastasize for another 3 to 5 weeks before regressing. Fibrosarcomas recurred 3 weeks to 8 months later in 8 of 12 persistently retroviremic cats with regressed tumors. Although the blood and bone marrow from these cats contained predominantly FeLV-helper, tumor cells yielded both FeSV and FeLV-helper. Of 53 animals, 3 developed recurrent fibrosarcomas 5 weeks to 8 months after all signs of tumors and retroviremia had disappeared. Cells cultured from these tumors appeared initially like normal fibroblasts and were virus nonproducers. After one to three passages in culture, however, cells became malignantly transformed and replicated both FeSV and FeLV-helper. Cultures of the bone marrow from these and other nonviremic cats with regressed tumors yielded only FeLV-helper.
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PMID:Biological behavior of tumors and associated retroviremia in cats inoculated with Snyder-Theilen fibrosarcoma virus and the phenomenon of tumor recurrence after primary regression. 631 86

The translation products of the Snyder-Theilen (ST) and Gardner-Arnstein (GA) strains of feline sarcoma virus (FeSV), termed gag-fes proteins, are high molecular weight polyproteins containing different amounts of the amino terminus of the feline leukemia virus (FeLV) gag gene-coded precursor protein linked to a similar sarcoma virus-specific polypeptide. Both polyproteins are phosphoproteins with indistinguishable in vitro associated tyrosine-specific protein kinase activities. The polyproteins are extremely hydrophobic proteins which are intimately associated with the plasma membrane fraction of transformed cells. Approximately 10% of the proteins are modified by glycosylation and expressed on the cell surface where they are accessible to lactoperoxidase-mediated radio-iodination and trypsinization. Cell surface localization of the polyproteins does not appear to be necessary for transformation. However, preliminary evidence suggests that the amount of FeLV p30 sequences at the amino end of the proteins may have some effect on the intracellular distribution of the gag-fes polyproteins and on the phenotype of the transformed cell.
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PMID:Association of the transforming proteins of the ST and GA strains of feline sarcoma virus and their in vitro associated protein kinase activities with cellular membranes. 632 Sep 92

The human germ-line positions of the oncogenes ABL, SIS, and FES, the cellular counterparts of the v-onc genes of Abelson murine leukemia virus, simian sarcoma virus, and feline sarcoma virus, respectively, have been determined by in situ molecular hybridization of 3H-labeled v-onc gene probes to meiotic pachytene chromosomes. The position of ABL at 9q34.1 corresponds to the breakpoint in chromosome 9 in the translocation that gives rise to the Philadelphia chromosome, t(9;22) (q34; q11); the position of SIS at 22q13.1 is distal to the breakpoint in this chromosome. FES at 15q26.1 is also distal to the breakpoint in chromosome 15 in the translocation commonly seen in acute promyelocytic leukemia, t(15;17) (q24;q22).
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PMID:Localization of the cellular oncogenes ABL, SIS, and FES on human germ-line chromosomes. 632 3

The nucleotide sequence of the gag gene of feline leukemia virus and its flanking sequences were determined and compared with the corresponding sequences of two strains of feline sarcoma virus and with that of the Moloney strain of murine leukemia virus. A high degree of nucleotide sequence homology between the feline leukemia virus and murine leukemia virus gag genes was observed, suggesting that retroviruses of domestic cats and laboratory mice have a common, proximal evolutionary progenitor. The predicted structure of the complete feline leukemia virus gag gene precursor suggests that the translation of nonglycosylated and glycosylated gag gene polypeptides is initiated at two different AUG codons. These initiator codons fall in the same reading frame and are separated by a 222-base-pair segment which encodes an amino terminal signal peptide. The nucleotide sequence predicts the order of amino acids in each of the individual gag-coded proteins (p15, p12, p30, p10), all of which derive from the gag gene precursor. Stable stem-and-loop secondary structures are proposed for two regions of viral RNA. The first falls within sequences at the 5' end of the viral genome, together with adjacent palindromic sequences which may play a role in dimer linkage of RNA subunits. The second includes coding sequences at the gag-pol junction and is proposed to be involved in translation of the pol gene product. Sequence analysis of the latter region shows that the gag and pol genes are translated in different reading frames. Classical consensus splice donor and acceptor sequences could not be localized to regions which would permit synthesis of the expected gag-pol precursor protein. Alternatively, we suggest that the pol gene product (RNA-dependent DNA polymerase) could be translated by a frameshift suppressing mechanism which could involve cleavage modification of stems and loops in a manner similar to that observed in tRNA processing.
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PMID:Nucleotide sequence of the gag gene and gag-pol junction of feline leukemia virus. 632 19

Selected populations of cats that were naturally exposed to the feline leukemia virus (FeLV) were found to have humoral antibodies to a normal cell protein designated NCP105. Earlier studies revealed that cats exposed to FeLV often had serum antibodies to the feline oncornavirus-associated cell membrane (FOCMA) as well as to a feline sarcoma virus (FeSV) -specific transforming protein designated gag-fes. Cats with no history of exposure to FeLV or FeSV lacked antibodies to all three antigens: NCP105, FOCMA, and gag-fes. Following exposure to FeLV, cats develop antibodies to either NCP105 or to gag-fes and FOCMA, but not to both groups of antigens. NCP105 is present in both normal and transformed cells from a wide variety of species. It lacks peptide homology with gag-fes and it is not a phosphoprotein. The presence of antibodies to NCP105 in cats exposed to FeLV but not in unexposed cats suggests that FeLV may activate the NCP105 gene or increase the relative immunogenicity of this protein in vivo.
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PMID:Infection with feline leukemia virus associated with induction of humoral response to a normal cell protein. 632 86

The nucleotide sequence encoding the transforming polyprotein of the McDonough strain of feline sarcoma virus was determined. This sequence includes 231 nucleotides specifying a leader peptide, 1,377 nucleotides encoding most of the feline leukemia virus-derived gag gene, and 2,969 nucleotides representing the viral transforming gene v-fms. A single open reading frame was predicted to encode a fusion polyprotein of 160,000 daltons (P160gag-fms). Fourteen potential sites for glycosylation were predicted within the v-fms-encoded portion of the protein, consistent with previous observations that the primary translation product is rapidly glycosylated. The presence of hydrophobic signal peptides within the amino-terminal leader sequence and in the middle of the v-fms-encoded moiety suggests that the transforming glycoprotein becomes oriented with its amino terminus within the lumen of the rough endoplasmic reticulum and its carboxyl terminus protruding across the membrane of the rough endoplasmic reticulum into the cytoplasm. The latter portion of the protein shows unexpected homology to tyrosine-specific protein kinases encoded by several of the known retroviral oncogenes.
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PMID:Nucleotide sequence of the feline retroviral oncogene v-fms shows unexpected homology with oncogenes encoding tyrosine-specific protein kinases. 658 85

The Gardner-Rasheed strain of feline sarcoma virus (GR-FeSV), is a recent isolate of a naturally occurring cat sarcoma. The primary translational product of GR-FeSV (GR P70) was shown to be a phosphoprotein with associated tyrosine-specific protein kinase activity. The relationship between the GR-FeSV provirus and once genes of other transforming retroviruses known to code for tyrosine kinases was examined by molecular hybridization. Probes repesenting onc genes of Snyder-Theilen and McDonough strains of feline sarcoma virus, Rous sarcoma virus, and Abelson murine leukemia virus did not detectably hybridize integrated GR-FeSV. These findings suggest that GR-FeSV contains a distinct tyrosine kinase-coding onc gene.
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PMID:Analysis of the primary translational product and integrated DNA of a new feline sarcoma virus, GR-FeSV. 660 28

Four cell lines producing transforming proteins encoded by three mammalian oncogenes (fes, abl, and ras) were investigated for incorporation of [3H]myristate into gag-onc fusion proteins. Using 5-min pulse-labelings, fusion proteins of Abelson murine leukemia virus, Gardner-Arnstein strain of feline sarcoma virus (FeSV), and Snyder-Theilen strain of FeSV were shown to be myristylated. In a 4-hr pulse, p29gag-ras of rat sarcoma virus (RaSV) was also shown to incorporate radiolabel. The fatty acid was recovered from this labeled protein by acid hydrolysis, and identified by reverse-phase thin-layer chromatography to be [3H]myristic acid. The results indicate that substitution of viral gag sequences by cellular oncogene sequences does not abolish their ability to become post-translationally modified by this long chain fatty acid (A. Schultz and S. Oroszlan, J. Virol. 46, 355-361). It is assumed that in the fusion proteins the myristyl moiety is linked through an amide linkage to the amino-terminal glycine as previously found for several retroviral gag precursor polyproteins (L. E. Henderson, H. C. Krutzsch, and S. Oroszlan, Proc. Natl. Acad. Sci. USA 80, 339-343). The possible role of myristylation of transforming proteins is discussed.
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PMID:Myristylation of gag-onc fusion proteins in mammalian transforming retroviruses. 660 21


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