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 production of Moloney murine leukaemia virus from chronically infected cells was inhibited after starvation of glutamine. While the rate of synthesis of the precursor of the core proteins, Pr65gag, was not affected in the starved cells, its proteolytic processing was blocked. Pulse-chase experiments indicated that glutamine was required during the synthesis of Pr65gag to facilitate its subsequent processing. In addition, the synthesis of Pr200gag-pol, the precursor of the protease, reverse transcriptase and endonuclease, was inhibited in the glutamine-starved cells. Starvation for other essential amino acids such as tyrosine and isoleucine affected neither the synthesis nor the processing of the virus proteins. These results suggest that the readthrough mechanism which enables synthesis of the Pr200gag-pol polyprotein is modulated in the chronically infected cells by glutamine levels. Since the viral protease is part of the pol gene, its synthesis may be inhibited in the glutamine-starved cells and Pr65gag is therefore not processed.
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PMID:Glutamine starvation of murine leukaemia virus-infected cells inhibits the readthrough of the gag-pol genes and proteolytic processing of the gag polyprotein. 348 14

A cDNA clone representing the gene encoding the beta chain of the human T-cell antigen receptor has been isolated recently. By using fragments of this cDNA as hybridization probes in Southern blot analysis of restriction endonuclease-digested genomic DNA, we have now examined the structure of the gene in DNA from 26 patients with acute leukemia and from 23 normal individuals. We have found that the T-cell antigen receptor gene has undergone somatic rearrangement in 14 of 14 patients with the phenotypic diagnosis of T-cell acute lymphoblastic leukemia. In this group of patients, similar patterns of rearrangement appear to occur in different patients. This finding suggests that there is either a limited repertoire of possible rearrangements or an association between the development of leukemia and specific patterns of rearrangement. DNA from 6 patients with acute myeloblastic leukemia, 6 patients with non-B, non-T acute lymphoblastic leukemia, and 23 nonleukemic individuals showed no rearrangement or polymorphism. One case of T-cell acute lymphoblastic leukemia, however, showed rearrangement of both the T-cell receptor beta chain and the constant region of the immunoglobulin gene. Studies with mixtures of DNAs from leukemic bone marrow cells and cultured skin fibroblasts, as well as with remission and relapse marrow DNAs from the same patients, indicate that this technique can detect 1% leukemic cells in a mixed population. In addition, DNA from the marrow of a patient in relapse contains a similar rearrangement to that found in the marrow sample taken at the time of diagnosis, which suggests that the original clone of leukemic cells was responsible for relapse. Our results indicate that assessment of rearrangement of the T-cell antigen receptor gene will be valuable in the diagnosis and management of leukemia and can be used to evaluate clonality in T-cell neoplasia.
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PMID:Somatic rearrangement of T-cell antigen receptor gene in human T-cell malignancies. 385 57

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

The template requirements and deoxyribonucleic acid (DNA) products of the DNA polymerases isolated from Rauscher leukemia and avian myeloblastosis viruses have been examined. All DNA preparations or synthetic polydeoxynucleotides which are active as primers possess a duplex structure containing single-stranded regions with a 3'-hydroxyl terminus. Native DNA and fully single-stranded DNA are inactive; moreover, their activity is not enhanced by sonic oscillation or treatment with micrococcal nuclease, Neurospora nuclease, or low levels of deoxyribonuclease I. Poor DNA templates are activated by treatment with exonuclease III, large amounts of deoxyribonuclease I, or an endonuclease isolated from Rauscher viral preparations. In reactions primed with deoxyadenylate-deoxythymidylate copolymer, the product formed is covalently attached to primer strands, indicating that no new strands are initiated. DNA polymerase products formed with exonuclease III- or deoxyribonuclase I-treated DNA are duplex structures. Short single-stranded regions are completely filled in, whereas long single-stranded regions are only partly repaired. DNA preparations containing extensive single-stranded regions are poorly utilized as templates.
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PMID:RNA-dependent DNA polymerase activity of RNA tumor viruses. I. Directing influence of DNA in the reaction. 433 38

Human T-cell leukemia virus (HTLV) is a family of related human T-lymphotropic retroviruses closely linked with certain human T-cell malignancies and associated with many cases of acquired immunodeficiency syndrome (AIDS). We isolated and molecularly cloned HTLV from patients with both types of clinical disorders and found by restriction endonuclease mapping and core and envelope protein analysis that at least two evolutionarily divergent viral subgroups exist, HTLV-I and HTLV-II. Previous studies have failed to detect significant nucleotide sequence homology between HTLV-I and HTLV-II even though these different members of the HTLV family share certain biologic properties such as T-cell tropism and transformation. To further test these viruses for conserved regions in their genomes, we examined hybridization between HTLV-I and HTLV-II by using Southern blotting and heteroduplex mapping at different melting points. These two techniques produced similar results, showing that HTLV-I and HTLV-II proviruses have, in fact, strongly conserved nucleotide sequences in the pX region and lesser although still substantial homology in the LTR, gag, pol, and env regions. These data provide experimental evidence that HTLV-II, like HTLV-I, contains pX sequences. Although the function of pX is unknown, its conservation in evolutionarily divergent human T-lymphotropic viruses implies a biologically important function. It is possible, but unproven, that pX could encode proteins involved in T-cell tropism, cell transformation, immune suppression, or other biologic actions characteristic of the HTLV family.
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PMID:Genomes of evolutionarily divergent members of the human T-cell leukemia virus family (HTLV-I and HTLV-II) are highly conserved, especially in pX. 608 32

RD-114 is a replication-competent, xenotropic retrovirus which is homologous to a family of moderately repetitive DNA sequences present at ca. 20 copies in the normal cellular genome of domestic cats. To examine the extent and character of genomic divergence of the RD-114 gene family as well as to assess their positional association within the cat genome, we have prepared a series of molecular clones of endogenous RD-114 DNA segments from a genomic library of cat cellular DNA. Their restriction endonuclease maps were compared with each other as well as to that of the prototype-inducible RD-114 which was molecularly cloned from a chronically infected human cell line. The endogenous sequences analyzed were similar to each other in that they were colinear with RD-114 proviral DNA, were bounded by long terminal redundancies, and conserved many restriction sites in the gag and pol regions. However, the env regions of many of the sequences examined were substantially deleted. Several of the endogenous RD-114 genomes contained a novel envelope sequence which was unrelated to the env gene of the prototype RD-114 env gene but which, like RD-114 and endogenous feline leukemia virus provirus, was found only in species of the genus Felis, and not in other closely related Felidae genera. The endogenous RD-114 sequences each had a distinct cellular flank which indicates that these sequences are not tandem but dispersed nonspecifically throughout the genome. Southern analysis of cat cellular DNA confirmed the conclusions about conserved restriction sites in endogenous sequences and indicated that a single locus may be responsible for the production of the major inducible form of RD-114.
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PMID:Molecular genetic characterization of the RD-114 gene family of endogenous feline retroviral sequences. 609 Jun 93

Integration and amplification of ecotropic and recombinant proviral sequences in high-molecular-weight cellular DNAs from ecotropic Gross virus-accelerated AKR thymomas were analyzed using an ecotropic-specific probe, p400, and an envelope-specific probe, pAKV-5. New ecotropic proviral sequences were detected at three sites in the DNAs from eight Gross virus-accelerated thymomas following EcoRI restriction endonuclease digestion and at six sites following PvuII restriction endonuclease digestion. The integration of these new ecotropic proviral sequences appeared to be random. Recombinant 3' proviral-cellular DNA junction fragments were detected at 30 sites following digestion with EcoRI. These new recombinant fragments ranged in size from 9.0 to 2.5 kb with 6/8 thymoma DNAs containing a fragment of 2.7 kb. PvuII generated new recombinant 3' proviral-cellular junction fragments that ranged in size from 12.5 to 2.1 kb with 5/8 thymoma DNAs containing a fragment of 2.5 kb. It appears that the leukemia-accelerating ecotropic Gross virus is responsible for the generation of a unique 3' recombinant proviral-cellular junction fragment. This fragment can be detected against a background of randomly integrated ecotropic and recombinant proviruses.
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PMID:Specific integration of recombinant proviral sequences in ecotropic Gross virus-accelerated AKR thymomas. 610 May 72

The primary structure analysis of the gag gene products of human T-cell leukemia virus (HTLV)-ICR has been nearly completed. A comparison of the amino acid sequences with the published nucleotide sequence of HTLV-IATK established that i) p19 which is known to share antigenic determinants with a protein present in normal thymic epithelium, is nevertheless virally coded. ii) The gene order and complete primary structure of the gag precursor (Pr55) which has been shown to be myristylated (My) at its N-terminus is My-p19-p24-p15-OH; and iii) the Pr55gag amino acid sequences of HTLV-ICR and HTLV-IATK are nearly identical showing only a single residue difference in the C-terminal region of p15. Antibodies to synthetic peptides inferred from the nucleotide sequence of the env gene of HTLV-IATK were also raised and used to identify and purify env precursor gPr62-68, surface glycoprotein gp46-51 and transmembrane protein p21. While most of the peptide sera were shown to be subgroup specific some of them detected antigenic determinants shared between protein homologs of viruses of subgroups I and II. Partial or complete amino acid sequences of both the gag and env gene coded proteins of bovine leukemia virus (BLV) structural proteins have also been determined. These extensive protein data together with nucleotide sequences confirm and extend our initial finding that HTLV and BLV are structurally and antigenically related and may have originated from common ancestor. The structural and immunological studies revealed also relationships between HTLV and a number of type C and type D retroviruses studied. One of the highly conserved sequences is shared by the transmembrane proteins of these retroviruses which have been implicated in immunosuppression. It is conceivable that these common regions have common biological function. Two previously unidentified proteins of BLV have also been purified and structurally characterized. Nucleotide sequences capable of coding for related products are present in HTLV. The nature and possible biological functions of these new BLV proteins and the putative HTLV gene products will be discussed. The size and complexity of the genome of the replication competent retroviruses are similar but not identical. The 35S RNA of all replication competent helper viruses is divided into three genes encoding the viral structural proteins: the gag (group-specific antigen) gene codes for the internal structural proteins, the pol (polymerase) gene codes for the enzymes protease, reverse transcriptase and endonuclease and the env (envelope) gene codes for the proteins of the viral envelope.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Structural and antigenic characterization of the proteins of human T-cell leukemia viruses and their relationships to the gene products of other retroviruses. 610 Jun 35

Four cloned rat cell lines (NX-1 to -4) infected with Moloney murine leukemia virus and defective in virus replication were found to be all different by viral protein and nucleic acid analyses. All four clones produced noninfectious particles and, except for NX-2, at about the same level as wild type. Compared with wild-type virions these defective particles contained larger amounts of gag precursor proteins and very little or no p30 or p15. Analysis of intracellular precursor proteins revealed that NX-2 to -4 synthesized normal Pr65gag, whereas NX-1 produced a slightly smaller precursor. Both NX-1 and NX-4 synthesized an intracellular polyprotein with a size similar to that of wild-type Pr180 gag-pol. Restriction endonuclease analysis of NX-1 to -4 cellular DNA showed that each clone contained a single integrated provirus which possessed large terminal repeat sequences at both the 5' and 3' ends. The proviruses of NX-1 to -3 appeared normal by restriction endonuclease analysis, but NX-4 provirus had a deletion of 1,700 base pairs comprising part of the polymerase region. The noninfectious particles produced by all four clones packaged Moloney viral RNAs and rat RNAs of two different sizes.
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PMID:Four Moloney murine leukemia virus-infected rat cell clones producing replication-defective particles: protein and nucleic acid analyses. 616 41

The Mn2+-dependent endonuclease activity associated with the avian myeloblastosis virus RNA-directed DNA polymerase has been shown to be activated by ATP in the presence of Mg2+. In the presence of Mn2+ the endonucleolytic activity was stimulated about 3-fold by the addition of ATP. The earlier identified Mr = 40,000 Friend murine leukemia virus (F-MuLV)-associated endonuclease which functions in the presence of both Mg2+ and Mn2+ has also been shown to be similarly stimulated by ATP. For both endonuclease activities stimulation was only observed at ATP concentrations above 0.5 mM, and it did not increase upon elevating the ATP concentration above 2.5 mM. ADP and dATP also stimulated both activities, although not to the same extent as ATP. GTP had no apparent effect and AMP seemed to inhibit both activities. The effect ATP analogs had on the F-MuLV associated endonuclease activity could suggest that the endonuclease reaction in the presence of ATP might involve the cleavage of beta-gamma phosphate bonds in ATP. Neither adenyl-5'-yl imidodiphosphate nor (beta, gamma-methylene)adenosine 5'-triphosphate stimulated the activity, whereas significant stimulation was observed in the presence of (alpha, beta-methylene)adenosine 5'-triphosphate. Although no ATPase activity could be detected in the purified F-MuLV endonuclease preparation, the data do not exclude the possibility that ATP may be cleaved in amounts which are equivalent to the number of nicks introduced into DNA by the virus-associated endonuclease. In the presence of ATP and Mg2+ the F-MuLV-associated endonuclease nicked both supercoiled and linear DNA duplexes extensively, although the former was nicked more readily than the latter. Single-stranded DNA functioned poorly as a substrate. The nicks introduced by the enzyme contained a 5'-phosphoryl terminus and a 3'-hydroxyl group.
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PMID:Effect of ATP on the Friend Murine leukemia virus-associated endonuclease activity and the endonuclease activity of the avian myeloblastosis virus RNA-directed DNA polymerase. 616 71


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