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)

Human T-cell leukemia virus type I (HTLV-I) contains a unique sequence pX that is located between env and the 3' long terminal repeat (LTR) and codes for three pX proteins, p40 chi, pp27 chi-III and pp21 chi-III. One of these proteins, p40 chi, was previously shown to activate transcription from the LTR in a trans-acting manner, which suggested that it activated some cellular genes involved in leukemogenesis. In this study, the sequences in the LTR responsible for this trans-activation were analyzed. Construction of deletion mutants of the LTR in pLTR-CAT and measurement of their activities in trans-activated expression of the CAT gene showed that sequences upstream of the TATA box were responsible for the trans-activation mediated by p40 chi. The active unit was identified as an enhancer sequence containing direct repeats by inserting it into an enhancer-minus SV40 promoter. Thus, it was concluded that an enhancer sequence in HTLV-I LTR is responsible, at least in part, for transcriptional trans-activation mediated by the viral product p40 chi.
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PMID:A transcriptional enhancer sequence of HTLV-I is responsible for trans-activation mediated by p40 chi HTLV-I. 301 23

Nucleotide sequence analysis of the cellular sequences flanking the integrated ecotropic (mouse-infectious) murine leukemia provirus of BALB/c mice indicated that the murine leukemia provirus is integrated in opposing transcriptional orientation within a solo long terminal repeat (LTR) of the VL30 family of endogenous retrovirus-related sequences. To quantify the effect of this integration event on the ability of the ecotropic provirus to be expressed, we constructed recombinant molecules that carried the chloramphenicol acetyltransferase (cat) gene and various viral LTRs and determined the CAT activity induced by these constructs after transfection of NIH 3T3 cells. Our results indicate that the BALB/c ecotropic LTR is about 10-fold more active than the VL30 LTR. The presence of the VL30 LTR did not affect the transcriptional activity of the ecotropic LTR in the context of the integration event. Our results also indicate that the LTRs of the BALB/c provirus are less transcriptionally active than are the proviral LTRs of AKR murine leukemia virus and the Harvey murine sarcoma virus.
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PMID:Germ line integration of a murine leukemia provirus into a retroviruslike sequence. 302 96

Human T-cell leukemia virus type I has a unique sequence, pX, between env and the 3' long terminal repeat (LTR). One of its products, p40, activates gene expression directed by the LTR in a trans-acting manner. We have analysed the mechanism of this trans-activation mediated by p40 in human T cells co-transfected with a plasmid expressing p40 using the transient CAT gene expression. We identified two distinct elements in the LTR which are involved in maximum gene expression. The first was present in a 230-bp fragment upstream from TATA box in the U3 region and behaved as a classical enhancer. This region was also shown to be responsible for trans-activation by p40. This element alone together with functional p40 could direct the gene expression at only approximately 10% of the level achieved by the complete LTR and p40. The second element was present within a 300-bp fragment downstream from the RNA start site and profoundly enhanced the gene expression in a way independent from trans-activation mechanism. This enhancement was observed only when the element was located immediately downstream from the RNA start site without orientation preference. These two elements participate independently in the enhancement of gene expression.
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PMID:Identification of two distinct elements in the long terminal repeat of HTLV-I responsible for maximum gene expression. 303 89

Cotransfection of cDNA encoding the trans-activator gene product of human T-cell leukemia virus, type I (HTLV-I) (tat-I), which acts in trans to augment viral gene expression, has revealed strong regulatory effects of this viral protein on the inducible cellular promoters governing human interleukin 2 (IL-2) and IL-2 receptor (Tac) gene expression. The tat-I protein stimulates a 3- to 6-fold increase in IL-2 receptor (Tac) promoter activity in transfected Jurkat T cells, but not in the natural killer-like YT cell line, as measured by changes in the expression of the chloramphenicol acetyltransferase (CAT; EC 2.3.1.28) reporter gene linked to this promoter. In contrast, tat-I alone has little or no effect on IL-2 promoter activity in Jurkat T cells but markedly synergizes with other mitogenic stimuli (phytohemagglutinin, phorbol 12-myristate 13-acetate, or the OKT3 monoclonal antibody), which alone are ineffective. The tat-I protein also partially circumvents the pronounced inhibitory effects of cyclosporin A on the IL-2 promoter. Other cellular and viral promoters are unaffected by the tat-I gene product, either alone or in combination with other mitogens. The specific effects of the tat-I gene product on the IL-2 and IL-2 receptor (Tac) promoters suggest the possibility of an autocrine or paracrine mechanism of T-cell growth as an early event in HTLV-I-mediated leukemogenesis.
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PMID:Activation of interleukin 2 and interleukin 2 receptor (Tac) promoter expression by the trans-activator (tat) gene product of human T-cell leukemia virus, type I. 303 48

Human T-cell leukemia virus type I (HTLV-I) encodes a trans-activator protein p40x which positively regulates transcription of the viral RNA as well as interleukin-2 and its receptor genes. We placed a cDNA coding for p40x in baculovirus Bombyx mori nuclear polyhedrosis virus (BmNPV) expression vectors. Infection of BmN cells derived from an insect, B. mori (silkworm), with a recombinant virus led to the production of soluble p40x. The biological activity of the recombinant p40x was demonstrated by introducing the protein into intact NIH 3T3 cells that had been selected for genomic integration of HTLV-I LTR connected with the CAT gene. Immunocytochemical and cell fractionation analyses showed the localization of p40x in both the cytoplasmic and nuclear fractions of BmN cells. Analyses of 32P-labeled proteins of BmN cells by cell fractionation and subsequent immunoprecipitation revealed that the p40x present in each subcellular fraction was phosphorylated. The post-translational modification was inhibited by the addition of a protein kinase inhibitor K252a during the metabolic labeling of BmN cells. Phosphoamino acid analysis indicated that the phosphorylation occurred on serine residues of p40x.
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PMID:Evidence for phosphorylation of trans-activator p40x of human T-cell leukemia virus type I produced in insect cells with a baculovirus expression vector. 305 77

The nucleotide sequence of the 3' long terminal repeat and adjacent viral and host sequences was determined for a bovine leukemia provirus cloned from a bovine tumor. The long terminal repeat was found to comprise 535 nucleotides and to harbor at both ends an imperfect inverted repeat of 7 bases. Promoter-like sequences (Hogness box and CAT box), an mRNA capping site, and a core enhancer-related sequence were tentatively located. No kinship was detected between this bovine leukemia proviral fragment and other retroviral long terminal repeats, including that of human T-cell leukemia virus.
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PMID:Nucleotide sequence analysis of the long terminal repeat of integrated bovine leukemia provirus DNA and of adjacent viral and host sequences. 631 64

In 20 Dutch children with acute lymphoblastic leukemia (ALL), Cu and Zn levels in cerebrospinal fluid (CSF) were studied during standard treatment (Protocol ALL-BFM-86/SNWLK-ALL-VII). CSF-Cu in 10 controls was 0.04 +/- 0.02 mumol/L, lower compared to values in adults. At the moment of diagnosis, CSF-Cu values were higher, 0.06 +/- 0.03 mumol/L, and during maintenance therapy lower, 0.01 +/- 0.01 mumol/L. Children with central nervous system (CNS) involvement ALL as judged by CAT Scan and EEG--in addition to cytology--showed lower CSF-Cu values compared to children without. CSF-Zn values were also measured. CSF-Zn was 0.05 mumol/L and did not vary. Cu/Zn molar ratios were increased at the onset of treatment, and decreased during maintenance therapy. The changes in CSF-Cu may follow the natural course of the disease or may relate to the success of treatment, reflecting a decrease of leukemia activity. Another explanation concerns a risk of CNS damage by low CSF-Cu causing neuron dysfunction. Conditions necessary for the interpretation of these results into a clinical strategy for followup study are outlined.
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PMID:Changes of CSF-Cu and -Zn in children with acute lymphoblastic leukemia. 750 42

The mechanism of repression of transcription by ELP, the embryonal long terminal repeat binding protein, was investigated. ELP represses the Moloney murine leukemia virus long terminal repeat by binding to a site which overlaps with a sequence element for retinoic acid receptor binding. This suggests possible competition of ELP with retinoic acid receptor for the same sequence elements. Oligonucleotides corresponding to ELP and/or retinoic acid receptor binding elements were placed upstream of the SV40 promoter and their effect on gene expression was analyzed by CAT assay. Elements which have affinity to both ELP and retinoic acid receptor were activated by retinoic acid receptor and these activations were repressed by ELP. An ELP binding element without affinity to retinoic acid receptor was insensitive to both activation by retinoic acid receptor and repression by ELP. Furthermore, cellular ELP binding elements and the Moloney leukemia virus long terminal repeat were activated by retinoic acid. These data suggest that one of the mechanism of transcriptional repression by ELP is competition for binding sites with transactivators such as retinoic acid receptors.
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PMID:Repression of retinoic acid-induced transactivation by embryonal LTR binding protein. 770 22

The human immunodeficiency virus type-1 (HIV-1) Tat activation response (TAR) region is essential for Tat-mediated trans-activation of the HIV-1 long terminal repeat (LTR). The TAR element is present on the 5' and 3' ends of all HIV-1 transcripts and is relatively conserved among different HIV-1 isolates. These properties make it an attractive target for anti-HIV-1 gene therapy strategies. We have constructed a Moloney murine leukemia-based retroviral vector that expresses a chimeric tRNA(iMet)-antisense TAR fusion transcript complementary to the HIV-1 TAR region. The potential of this anti-TAR retroviral vector to inhibit HIV-1 was initially tested by transient transfections with an HIV-1-LTR-Tat expression plasmid into HeLa-CAT cells. Anti-TAR inhibited Tat-mediated HIV-1 LTR-driven CAT reporter gene expression in a dose-dependent fashion. The antisense-TAR vector was then used to transduce the human SupT1 T cell line. Cotransfection of these SupT1 cells with a Tat expression plasmid plus an HIV-1 LTR-CAT reporter plasmid resulted in decreased CAT gene expression in comparison to control transduced SupT1 cells. The antisense-TAR engineered SupT1 cell line was then challenged with HIV-1MN.HIV-1 viral production was inhibited in SupT1 cells transduced with the antisense-TAR retroviral vector. Greater inhibition of HIV-1 was observed with antisense-TAR as compared to antisense-Tat expressing retroviral vector. These observations suggest that antisense-TAR retroviral vectors are potentially useful for clinical anti-HIV-1 gene therapy.
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PMID:Inhibition of human immunodeficiency virus type-1 by retroviral vectors expressing antisense-TAR. 771 Nov 39

We have examined the expression of the interleukin 1 beta (IL-1 beta) gene during the granulocytic differentiation of two promyeloid leukemia cell lines, HL-60 and NB4. HL-60 is known to differentiate along the granulocytic pathway after treatment with 13-trans-retinoic acid (13-trans-RA), whereas treatment with phorbol myristate acetate (PMA) leads to development of mature macrophages. NB4 cells are derived from the bone marrow of an acute promyelocytic leukemia (APL) patient in relapse, have a translocated RA receptor-alpha, and are converted into nondividing granulocytes by 13-trans-RA treatment. When HL-60 or NB4 were cultured in the presence of 13-trans-RA, IL-1 beta mRNA and protein levels were increased. In the more mature THP-1 cells which are induced to macrophage-like cells by 13-trans-RA treatment, RA was unable to induce any IL-1 beta expression, implying that the effect of 13-trans-RA is associated with granulocytic differentiation. Moreover, PMA and 13-trans-RA had a strong synergistic effect in the induction of IL-1 beta gene expression. Nuclear run-off analysis indicated that the increased IL-1 beta gene expression was due to an enhanced rate of transcription. When the cells were transfected with an IL-1 beta-X-CAT reporter plasmid containing the -2982/-2748 promoter segment of the IL-1 beta gene conferring responsiveness to PMA, both NB4 and HL-60 cells responded with increased CAT activity when stimulated with 13-trans-RA alone. In contrast to PMA, 13-trans-RA was unable to increase AP-1 enhancer activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activation of interleukin-1 beta gene expression during retinoic acid-induced granulocytic differentiation of promyeloid leukemia cells. 781 35


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