Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nucleotide sequence of the pol-env intergenic region of two isolates of caprine arthritis-encephalitis virus (CAEV) was determined. Two open reading frames (orfs) were identified, designated Q and S by homology with visna virus. CAEV orf S is a single exon encoding a deduced 87-amino acid gene product sharing 36 amino acid identities with the visna trans-acting transcriptional activator (Tat). Ten of these identities comprise a conserved CGCRLCNPGW sequence similar to a cysteine-rich domain essential for trans-activation by human immunodeficiency virus Tat. To determine if transcription promoted by the CAEV long terminal repeat (LTR) could be stimulated in CAEV-infected goat synovial membrane cells, a plasmid (pCAE-CAT) expressing bacterial chloramphenicol acetyltransferase (CAT) under control of the CAEV LTR was transfected into uninfected and infected cells. Sixfold enhancement of CAT activity was observed in infected cells using 100 ng of transfected plasmid. To determine if the pol-env region encodes a gene product which trans-activates the CAEV LTR, goat synovial membrane cells were cotransfected with pCAE-CAT and pRSV-1.9, a plasmid expressing the pol-env region under control of the Rous sarcoma virus LTR. Results indicated that the CAEV genome encodes a tat gene product attributable to orf S.
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PMID:Genetic structure of the pol-env region of the caprine arthritis-encephalitis lentivirus genome. 184 32

HTLV-I, II, HIV-1, 2 and other retroviruses possess genes for the transcriptional activators, tax and tat, the expression of which is closely related with the pathogenesis of leukemia and human immunodeficiency syndrome (AIDS) and induced by the virus infection. The effects of these activators on the expression of host cell genes, however, are still largely unknown. Recently the authors have discovered that infection with HIV or Mo-MuLV causes a specific acceleration of the synthesis of an UAG suppressor glutamine tRNA in the host cell; they could demonstrate that this phenomenon is based on transcriptional promotion of tRNA genes which is due to a new transcriptional activator synthesized as a function of viral infection and/or increased virus levels. The present paper discusses the significance of the suppressor tRNA and explains the role of the virus in the regulation of its expression.
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PMID:Cell biological aspects of HIV-1 infection: effect of the anti-HIV-1 agent Avarol. 189 96

Sera from 39,898 blood donors were tested for HTLV-1 antibodies using two enzyme immunoassays (EIA). Sera testing initially reactive (IR) were retested in duplicate by both EIAs. Sera testing repeatedly reactive (RR) were further tested by two Western blots (WB) and by two radioimmunoprecipitation assays (RIPA). There were 176 (0.44%) EIA IR and 68 (0.17%) RR results. On WBs, 10 of the 68 EIA RR sera demonstrated reactivity to HTLV-1 gag gene-encoded core protein p24, with or without reactivity to other core proteins (p19, p28, p53/55). These ten sera were the only ones demonstrating reactivity on RIPAs to other HTLV-1 gene products - env gene-encoded glycoproteins gp46, gp61/68, or tat gene-encoded HTLV-1 transcriptional activator p40x. These ten sera were interpreted as positive for HTLV-1 antibodies. Of the remaining 58 EIA RR sera, 21 were negative by WBs and RIPAs, 37 sera demonstrated reactivity to various combinations of p19, p28, and p53/55, but not to p24 on WBs. These 37 sera were interpreted as "indeterminate", because they were negative by RIPAs. We conclude that: 1) EIA testing and WB/RIPA verification identified 10 (0.025%) HTLV-1 infected individuals among 39,898 low-risk blood donors; 2) anti-p24 may be a more sensitive and specific indicator of HTLV-1 infection than antibodies to p19, p28, or p53/55; and 3) presently, both WB and RIPA are needed to verify HTLV-1 EIA reactivity.
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PMID:Detection of antibodies to human T-lymphotropic virus type 1 (HTLV-1). 283 83

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

Apoptosis is an important regulatory process during normal development and maturation. We find that the proliferation-arresting and differentiation-inducing compound sodium n-butyrate (NaB) triggers a marked host chromatin degradation. This apoptotic process is independent of, but commensurate with, a rapid increase in viral mRNA synthesis and subsequent release of HIV-1 virus in transformed human cell lines harboring tat- (HLM1) or tat+ (U1, ACH-2) dormant HIV-1 proviruses. This compound stimulates a reversible accumulation of the characteristic viral mRNAs at a much faster rate than two other DNA degradation inducers such as tumor necrosis factor-alpha and phorbol 12-myristate 13-acetate. The transcriptional activator butyrate analogue, alpha-amino-n-butyrate, failed to cause similar phenotypic changes. These results suggest that common regulatory signals may be involved in activation of apoptosis genes and latent provirus by NaB.
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PMID:Induction of developmentally programmed cell death and activation of HIV by sodium butyrate. 800 66

We developed a sensitive vector system for the analysis of weak promoter activities. This promoter assay is based on the transcriptional activator protein, Tat, of human immunodeficiency virus type 1 (HIV-1). High-level expression of HIV requires activation in trans by Tat of the promoter in the long terminal repeat (LTR). Here we describe the construction of a promoterless pTat vector. Foreign promoter elements can be inserted upstream from the tat gene, and expression of Tat protein is measured in trans on a co-transfected LTR-CAT reporter plasmid. We show that this binary system is more sensitive than standard pCAT reporter assays.
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PMID:A sensitive promoter assay based on the transcriptional activator Tat of the HIV-1 virus. 803 9

Certain members of the lentivirus subfamily of retroviruses encode unique transcriptional activator (Tat) proteins that modify the transcription complex after binding to the 5' end of nascent viral mRNA. The Tat proteins are modular, containing RNA-binding and activation domains that can be exchanged between different Tat proteins or replaced with heterologous protein fragments. While there is considerable sequence conservation among the divergent Tat proteins, there are also some structural differences that might be informative. For example, a cluster of basic amino acids in HIV-1 Tat is sufficient for RNA binding in vivo and in vitro. The homologous region of EIAV Tat is necessary but not sufficient for recognition of its cognate cis-acting RNA element; the entire C-terminal 26 amino acids of EIAV Tat, including the basic patch, are required. To better understand the structure-function relationships in EIAV Tat, we have generated a battery of expression plasmids encoding insertion, deletion, and missense mutations in the carboxy-terminal region of the tat gene. The plasmids were tested for their ability to trans-activate the EIAV promoter or to trans-inhibit a heterologous Tat protein. A mutation of a glutamine to an arginine in the cluster of basic residues generated a potent trans-dominant inhibitor of both EIAV and HIV-1 Tat, indicating that the mutation abolished RNA binding but did not alter the activation domain. Mutations at the extreme C-terminus of EIAV Tat impaired both RNA binding and activation domain functions, suggesting effects on secondary or tertiary structure.
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PMID:Mutagenesis of EIAV TAT reveals structural features essential for transcriptional activation and TAR element recognition. 838 74

We previously demonstrated that after transduction with the v-Ha-ras oncogene and grafting onto nude mouse hosts, primary epidermal keratinocytes with a null mutation in the p53 gene form tumors with increased growth rates and predisposition to malignant conversion relative to p53 wild-type keratinocytes (Weinberg WC, et al., Cancer Res 54:5584-5592, 1994). To further explore the cooperation between p53 loss of function and activation of the ras oncogene, cell lines were established from the normal epidermises of newborn and adult p53-null mice, and parallel subclones were reconstituted with the p53val135 temperature-sensitive mutant. Reconstituted lines C, G, N, and V demonstrated functional p53 transcriptional activator activity at the wild-type-permissive temperature of 32 degrees C, compared with the hygromycin-selected control line X and parental p53-null lines NHK4 and AK1b. Hygromycin-selected subclones, but not the parental lines, made normal skin in vivo; all cell lines made carcinomas after introduction of v-Ha-ras, independent of p53 status. These cell lines were compared in vitro at 32 degrees C to maximize the amount of p53val135 in the wild-type conformation. Expression of v-Ha-ras did not consistently alter p53-mediated transcriptional activity, suggesting tat ras acts downstream or independently of p53. No correlation was observed between p53-mediated transcriptional activity and in vitro growth rates, colony formation after exposure to ultraviolet light, or suppression by normal neighboring keratinocytes. However, keratinocyte cell lines devoid of p53 and expressing v-Ha-ras formed colonies in soft agar; this was blocked at 32 degrees C in all cell lines reconstituted with p53val135. These keratinocyte lines provide a model for exploring the role of p53 and the interaction of p53 and ras in keratinocyte transformation.
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PMID:Cooperation of p53 loss of function and v-Ha-ras in transformation of mouse keratinocyte cell lines. 947 71

Human herpesvirus-8 (HHV-8) is a lymphotropic virus associated with several AIDS-related neoplasms. Two ORFs play a critical role in the regulation of virus replication: ORF50, encoding an immediate-early transcriptional activator, and ORF57, encoding a post-transcriptional regulator. We analysed their effects on the activation of the human immunodeficiency virus type 1 (HIV-1) LTR. ORF50 interacted synergically with tat, inducing a 10-fold enhancement of HIV-1 LTR transactivation. This effect occurred both in BCBL-1 cells, latently infected with HHV-8, and in HL3T1 cells, an epithelial cell line non-permissive to HHV-8 infection. Also, ORF57 enhanced tat-induced transactivation of HIV-1 LTR, but only in BCBL-1 cells, suggesting that its action was likely mediated by the induction of other viral functions. Finally, when both ORFs were expressed, the enhancement of transactivation induced by ORF50 was partially inhibited. The findings suggest that ORF57 can modulate ORF50 activity and that ORF50 may render biologically active small amounts of tat.
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PMID:Human herpesvirus-8 (Kaposi's sarcoma-associated herpesvirus) ORF50 interacts synergistically with the tat gene product in transactivating the human immunodeficiency virus type 1 LTR. 1145 4

The expression of HLA class II genes is under the control of a transcriptional activator, CIITA, encoded by the AIR-1 locus. Here we show that CIITA inhibits HIV-1 LTR transactivation mediated by Tat. The inhibition occurred when CIITA and Tat were transiently expressed in cells after transfection and, most importantly, when tat cDNA was transfected in cells expressing CIITA in a constitutive fashion and at physiological levels. Furthermore, CIITA inhibited the HIV-1 LTR transactivation mediated by extracellular Tat protein. CIITA inhibition of Tat function could be reversed by overexpression of Cyclin T1, the cellular cofactor used by Tat to facilitate elongation of viral transcripts. CIITA inhibition of Tat function had a dramatic effect on HIV-1 productive infection of human T cells because CIITA(+) T cells supported very poorly, if any, viral replication. These results indicate that sustained expression of CIITA in HIV-1-susceptible targets may down-regulate viral expression both in cells actively replicating the virus and in silently infected cells requiring exogenous Tat to reactivate virus from latency.
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PMID:The HLA class II transcriptional activator blocks the function of HIV-1 Tat and inhibits viral replication. 1235 30


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