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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The highly leukemogenic avian retrovirus E26 expresses the two transcriptional activator-type oncogenes v-myb and v-ets as a nuclear fusion protein. Previous studies have shown that both oncogenes cooperate in the transformation of erythroid cells in vitro and that the phenotypes of transformed cells differ, depending on whether the oncogenes are coexpressed as separate proteins or as a fusion protein. Here we show that virus constructs encoding either v-Myb or v-Ets as their only oncoprotein are nonleukemogenic and that constructs coexpressing nonfused v-Myb and v-Ets proteins appear to be weakly leukemogenic. Surprisingly, leukemic animals injected with the latter contain highly leukemogenic variant viruses that exhibit internal deletions in their genome, resulting in the synthesis of novel Myb-Ets fusion proteins. These results show that v-Myb and v-Ets must be fused to cause leukemia and establish a new mechanism of oncogene activation and cooperation.
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PMID:Fusion of the nuclear oncoproteins v-Myb and v-Ets is required for the leukemogenicity of E26 virus. 207 Apr 21

The transcriptional activator protein (Tax) from human T-cell leukemia virus type 1 was expressed in yeast using several different promoters in several strains: In all instances, expression of Tax resulted in very strong aggregation of the yeast cells. This phenotype appears to be identical by all criteria tested to the flocculation phenotype of the dominant mutation flo 1. Of most significance, mutations in Tax that affect transactivation of the IL-2R alpha regulatory sequences, but retain their ability to activate the viral long terminal repeat also fail to yield the aggregation phenotype. Based on these findings, expression of Tax in yeast may prove to be a simple primordial system for examining the regulatory mechanisms and cellular functions involved in regulation of gene expression.
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PMID:Expression of the HTLV-I tax transactivator in yeast: correlation between phenotypic alterations and tax function in higher eukaryotes. 207 11

We present the first report of a T-helper cell line, HUT 102, constitutively producing both granulocyte-macrophage colony-stimulating factor (GM-CSF) and monocytic colony-stimulating factor (M-CSF), as detected by sensitive enzyme-linked immunosorbent assays and Northern blot analysis. However, neither amplification nor structural change of the GM-CSF and M-CSF genes was detected by Southern blot analysis. In the case of HUT 102, in which human T-lymphotropic leukemia virus type I (HTLV-I) is integrated, the viral protein, which acts as a trans-acting transcriptional activator, may induce the production of both GM-CSF and M-CSF.
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PMID:Both granulocyte-macrophage colony-stimulating factor and monocytic colony-stimulating factor are produced by the human T-cell line, HUT 102. 214 80

Visna virus is an ungulate lentivirus that is distantly related to the primate lentiviruses, including human immunodeficiency virus type 1 (HIV-1). Replication of HIV-1 and of other complex primate retroviruses, including human T-cell leukemia virus type I (HTLV-I), requires the expression in trans of a virally encoded post-transcriptional activator of viral structural gene expression termed Rev (HIV-1) or Rex (HTLV-I). We demonstrate that the previously defined L open reading frame of visna virus encodes a protein, here termed Rev-V, that is required for the cytoplasmic expression of the incompletely spliced RNA that encodes the viral envelope protein. Transactivation by Rev-V was shown to require a cis-acting target sequence that coincides with a predicted RNA secondary structure located within the visna virus env gene. However, Rev-V was unable to function by using the structurally similar RNA target sequences previously defined for Rev or Rex and, therefore, displays a distinct sequence specificity. Remarkably, substitution of this visna virus target sequence in place of the HIV-1 Rev response element permitted the Rev-V protein to efficiently rescue the expression of HIV-1 structural proteins, including Gag, from a Rev- proviral clone. These results suggest that the post-transcriptional regulation of viral structural gene expression may be a characteristic feature of complex retroviruses.
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PMID:Visna virus encodes a post-transcriptional regulator of viral structural gene expression. 217 Sep 81

Human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) have two nonstructural trans-acting regulatory genes, tax and rex, located in the 3' region of the viral genome. The tax gene product (HTLV-I p40tax and HTLV-II p37tax) is the transcriptional activator of the viral long terminal repeat. The rex gene encodes two protein products, p27rex/p21rex and p26rex/p24rex in HTLV-I and HTLV-II, respectively. Rex acts posttranscriptionally to facilitate accumulation of full-length gag/pol and singly spliced env mRNA in the cytoplasm of HTLV-infected cells. Previous studies showed that the first ATG of the rex gene is critical for Rex production and function. The importance of the internal ATGs to Rex function is not known. However, in vitro mutagenesis of the HTLV-I rex gene has provided indirect evidence which suggests that p21rex, and by analogy HTLV-II p24rex, results from initiation at an internal AUG of the tax/rex mRNA. By using an infectious molecular clone of HTLV-II, we investigated the importance of the internal ATGs of the rex gene on Rex protein production and function. Our results indicate that p24rex of HTLV-II is not initiated at an internal AUG and that the internal methionine codons are not crucial to the function of the rex gene and, ultimately, the transforming properties of the virus.
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PMID:The internal methionine codons of human T-cell leukemia virus type II rex gene are not required for p24rex production or virus replication and transformation. 239 33

The Tax protein of human T-cell leukemia virus is a potent transcriptional activator of viral and cellular genes, including the genes for interleukin 2 and interleukin 2 receptor alpha chain (IL2R alpha). The NF-kappa B protein has been implicated in Tax-mediated activation of IL2R alpha gene expression. We show that activation of NF-kappa B by Tax is an indirect process that requires prior activation of a preexistent factor that is present in lymphoid cells. Deletion mutagenesis revealed that the carboxyl-terminal acidic region of Tax is required for activation of IL2R alpha-directed gene expression but dispensable for activation of the long terminal repeat (LTR). Our findings suggest that activation of viral and cellular gene expression by Tax is achieved through a cascade of events that involves multiple protein-protein associations and that the specificity of these associations is conferred through different domains of the Tax protein.
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PMID:Activation of NF-kappa B by the HTLV-I trans-activator protein Tax requires an additional factor present in lymphoid cells. 248 94

Human T-cell leukemia virus type 1 (HTLV-1) has two trans-acting regulator genes, tax and rex, in the pX region. The tax gene is a trans-acting transcriptional activator of the long terminal repeat (LTR) and also of the cellular gene for IL-2R alpha. The latter seems to explain initiation of abnormal growth of HTLV-1 infected cells. The rex gene is a posttranscriptional regulator accumulating gag and env mRNA and also indirectly suppressing the transcription. The regulation requires two cis-acting elements, the LTR sequence at the 3' terminus and 5' splice signal, suggesting a novel mechanism of RNA processing in the nucleus. These two trans-activator genes are essential for efficient replication of HTLV-1 and also explain its poor replication competence and tendency to be latent in vivo.
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PMID:Molecular mechanisms of regulation of HTLV-1 gene expression and its association with leukemogenesis. 269 36

One potent transcriptional activator of human T-cell leukemia virus type I (HTLV-I) is virally encoded protein Tax (p40x). p40x trans-activates HTLV-I through the long terminal repeat (LTR) by using a triply repeated 21-base-pair sequence as the target. In this report we have characterized the induction of the HTLV-I LTR by 12-O-tetradecanoylphorbol-13-acetate (TPA). By assaying progressively deleted mutations in the HTLV-I LTR, we have delimited a 60-base-pair sequence in the LTR which is capable of conferring TPA responsiveness, but not p40x responsiveness, to heterologous promoters in a position-independent fashion. This HTLV-I TPA-responsive element is specifically recognized by preexisting factors from uninfected cells. We show that activation of this sequence by phorbol ester does not require de novo cellular protein synthesis. When the HTLV-I LTR was simultaneously activated by both Tax and TPA, an additive effect was seen. This suggests the use of distinct regulatory pathways by the two respective trans-activators.
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PMID:Activation of the human T-cell leukemia virus type I long terminal repeat by 12-O-tetradecanoylphorbol-13-acetate and by tax (p40x) occurs through similar but functionally distinct target sequences. 278 91

Gene expression of human T-cell leukemia virus type 1 (HTLV-1) is regulated by two trans-acting factors encoded by the pX region, p40tax and p27tax.p40tax is a transcriptional activator and p27rex is a post-transcriptional regulator. Using full-length viral DNA, we studied the regulatory effects of rex on HTLV-1 gene expression. p27rex is required for expression of both gag and env proteins, increasing the level of their mRNAs. The effect was dependent on the dose of p27rex expression plasmid. In parallel, increased doses of p27rex suppressed the expression of fully spliced pX mRNA, which encodes the regulatory proteins. These two effects of p27rex operated at the post-transcriptional level and were independent of transcriptional regulation. Lowering the level of pX mRNA down-regulates transcription of the proviral genome. These observations demonstrate that rex is a positive post-transcriptional regulator for gag, pol and env protein expression, and acts at the same time as an indirect negative regulator of viral transcription.
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PMID:Post-transcriptional regulator (rex) of HTLV-1 initiates expression of viral structural proteins but suppresses expression of regulatory proteins. 283 30

Expression of the interleukin-2 receptor (IL-2R alpha) gene is activated by the transcriptional activator protein, Tax (previously referred to as the tat gene product), encoded by the human T-cell leukemia virus (HTLV-I). Multiple protein binding sites for specific DNA-protein interactions were identified over the upstream IL-2R alpha transcriptional regulatory sequences. However, only one region, which includes the sequence motif GGGGAATCTCCC, was required for activation by both the tax gene product and mitogenic stimulation. Remarkably, this sequence also bound the nuclear factor NF kappa B, which is important for induction of kappa-immunoglobulin gene expression. A model is presented whereby regulation of cellular gene expression by the HTLV-I tax gene product occurs via an indirect mechanism that may involve a post-translational modification of preexistent cellular transcription factors.
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PMID:Cellular transcription factors and regulation of IL-2 receptor gene expression by HTLV-I tax gene product. 283 5


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