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

The herpes simplex virus type 1 (HSV-1) ICP4 protein is a transcriptional activator of many eucaryotic RNA polymerase II promoters. The HSV-1 thymidine kinase gene (tk) promoter is induced by ICP4 and contains binding sites for the cellular transcription factors TFIID, Sp1, and CCAAT-binding proteins, each of which affects expression of the tk gene. In this study, the effects of mutations in these sites on the transcription of tk in the presence and absence of ICP4 were determined during viral infection. Only the TATA box was necessary for efficient expression in the presence of ICP4; however, ICP4 apparently can still induce tk transcription even when the TATA box is disrupted. Alteration of the Sp1 sites had a minor effect on ICP4-induced expression in comparison to a large effect in the absence of ICP4, indicating that ICP4 can operationally substitute for the function of the transcription factor Sp1. In addition, tk was still expressed with the kinetics of an early gene in the absence of binding sites for Sp1 and CCAAT-binding proteins.
 ...
PMID:Herpes simplex virus transactivator ICP4 operationally substitutes for the cellular transcription factor Sp1 for efficient expression of the viral thymidine kinase gene. 184 84

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.
 ...
PMID:Cell biological aspects of HIV-1 infection: effect of the anti-HIV-1 agent Avarol. 189 96

The IE-1 gene of Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV) was mapped between 95.7 and 97.1 map units on the viral genome. Sequence analysis of the OpMNPV IE-1 gene (OpIE-1) identified an open reading frame that coded for a predicted protein of 560 amino acids with a molecular weight of 64,775. Transcriptional analysis of OpMNPV-infected Lymantria dispar (LD652Y) cells identified two RNAs homologous to the OpIE-1 open reading frame that were 1.7 and 1.9 kb in size. The 1.7-kb transcript could be detected by 0 hr postinfection (hr p.i.) and the steady-state levels increased up to 48 hr p.i. The 1.9-kb message appears to be spliced and has peak expression from 4 to 6 hr p.i. but can still be detected at late times p.i. Comparison of the OpIE-1 and Autographa californica multicapsid nuclear polyhedrosis virus (AcMNPV) IE-1-predicted proteins revealed that the N-terminal region had very low sequence identity (21%) but had maintained an acidic profile, whereas the C-terminal region showed 55% amino acid identity. Transient assay analysis showed that OpIE-1 was able to trans-activate the AcMNPV delayed early reporter gene construct p39CAT in both LD652Y cells and Spodoptera frugiperda (Sf9) cells. The expression of p39CAT trans-activated by OpIE-1 was also found to be enhanced by the AcMNPV hr enhancer sequences. The OpIE-1 promoter was linked to the chloramphenicol acetyl transferase gene and deletion analysis was used to identify regions involved in the regulation of this gene. This analysis revealed that the OpIE-1 promoter contained regions that were responsive to a transcriptional activator that was specific to Sf9 cells. In addition it was shown that OpIE-1 could trans-activate its own promoter and that for maximal expression this required sequences between -420 and -330 relative to the transcriptional start site. These data suggest that OpIE-1 is autoregulated during normal viral infection of insect cells.
 ...
PMID:Identification and characterization of the IE-1 gene of Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus. 198 81

The tax gene product (Tax protein) of human T-cell leukemia virus type I (HTLV-I) is a specific transcriptional activator of the viral long terminal repeat sequence and is essential for the replication cycle of the virus. To elucidate the relationship between the presence of anti-Tax antibody and the transmission of the viral infection, annual consecutive serum samples from married couples serologically discordant or concordant for HTLV-I were examined. These included 5 individuals whose spouses seroconverted during this 5-year follow-up study period. The samples were tested by a Western blot assay using a recombinant Tax protein as the antigen. The results showed that 24 of 32 (75%) men in the concordant couples (both husband and wife were HTLV-I carriers) had anti-Tax antibody, while only 5 of 18 (27.8%) men in the discordant couples (husband was carrier and wife was seronegative to HTLV-I) were positive for anti-Tax antibody (P = 0.0012). Furthermore, all spouses of the 5 seroconverters (4 women and 1 man) had anti-Tax antibody, while only 23 of 46 (50%) age-matched randomly selected HTLV-I carriers from the discordant-couple group had anti-Tax antibody. When the data were analyzed by gender, all husbands of the female seroconverters had anti-Tax antibodies, which was significantly higher than the prevalence of anti-Tax antibodies in men who did not transmit the virus to their spouses during the follow-up period (P = 0.017). In addition, antibody reactivity to other HTLV-I antigens (including Env gp46, transmembrane protein gp21, and Gag p19 and p24) were examined. The results indicated no significant differences between the prevalence of antibody reactivity to any of the antigens in the spouses of the seroconverters and the reference group. We conclude that the presence of anti-Tax antibody in men may indicate a high risk of viral transmission to their wives via heterosexual routes.
 ...
PMID:Sexual transmission of human T-cell leukemia virus type I associated with the presence of anti-Tax antibody. 199 21

Permissiveness to replication of human immunodeficiency virus (HIV) differs in T lymphocytes and macrophages. In T cells, HIV transcription is poorly detected in vivo. Cloned, normal T lymphocytes show very little, if any, basal activity of the HIV enhancer and low nuclear expression of NF-kappa B, a potent transcriptional activator of the HIV enhancer. In contrast, fixed tissue macrophages express detectable HIV proteins, indicating permanent virus transcription. One explanation for the perpetuation of virus infection in macrophages could be sustained nuclear NF-kappa B expression. However, the U937 monocytic cell line, which is fully permissive to HIV replication, is known to express only low levels of nuclear NF-kappa B. We show here that chronic HIV infection results in both induction of a nuclear factor with antigenic properties indistinguishable from those of NF-kappa B and permanently increased HIV enhancer activity. This phenomenon, which is independent of tumour necrosis factor, is associated with HIV replication, and is thus likely to explain at least in part the perpetuation of HIV infection in monocytes.
 ...
PMID:HIV enhancer activity perpetuated by NF-kappa B induction on infection of monocytes. 202 29

Interferon-beta (IFN-beta) gene is transcriptionally activated following virus infection of various cell types such as fibroblasts. In the previous studies, regulatory DNA sequences that mediate the virus-induced transcriptional activation have been identified within the 5'-flanking region (up to around -117 respect to the CAP site) of the human IFN-beta gene. The sequences contain binding sites (-100 to -61) for a transcriptional activator, IRF-1, the gene of which is also virus-inducible. In the present study, we focused on an additional cis-element, located between the IRF-1 binding sites and TATA box. Interestingly, the element coincides with the previously identified elements for the transcription factors H2TF-1 and NF kappa B. The element, when tandemly repeated, functions in activating the distal gene expression in either constitutive or virus-inducible manner depending on the cell type. The results suggest the importance of cooperation between IRF-1 and H2TF-1/NF kappa B-like factor in the maximal IFN-beta gene induction.
 ...
PMID:Involvement of a cis-element that binds an H2TF-1/NF kappa B like factor(s) in the virus-induced interferon-beta gene expression. 256 73

The nuclear localization of the herpes simplex virus transcriptional activator protein ICP4 was studied by indirect immunofluorescence. At early times after viral infection, ICP4 quickly localized to a diffuse intranuclear distribution. ICP4 later concentrated in globular compartments within the nucleus. The redistribution to the compartments was dependent on viral DNA replication. Double staining for ICP4 and ICP8, the early major DNA-binding protein, revealed that both were found in the same intranuclear globular compartments at late times. These were previously named "replication compartments" (M. P. Quinlan, L. B. Chen, and D. M. Knipe, Cell 36:857-868, 1984). Because ICP4 and ICP8 are known to function in transcriptional activation and DNA replication, respectively, both DNA replication and late transcription may occur in these compartments. The association of ICP4 and ICP8 with the replication compartments appeared to be independent in that the retention of ICP8 in the compartments required ongoing viral DNA synthesis, while the association of ICP4 was independent of viral DNA synthesis once the compartments were formed. Because ICP4 shows a different distribution at early and late times, stimulation of transcription by ICP4 may involve different molecular events or contacts during these two periods of the replicative cycle.
 ...
PMID:Stages in the nuclear association of the herpes simplex virus transcriptional activator protein ICP4. 302 60

The human hepatitis B virus (HBV) HBx protein is a small transcriptional activator that is essential for virus infection. HBx is thought to be involved in viral hepatocarcinogenesis because it promotes tumorigenesis in transgenic mice. HBx activates the RAS-RAF-mitogen-activated protein (MAP) kinase signaling cascade, through which it activates transcription factors AP-1 and NF-kappa B, and stimulates cell DNA synthesis. We show that HBx stimulates cell cycle progression, shortening the emergence of cells from quiescence (G0) and entry into S phase by at least 12 h, and accelerating transit through checkpoint controls at G0/G1 and G2/M. Compared with serum stimulation, HBx was found to strongly increase the rate and level of activation of the cyclin-dependent kinases CDK2 and CDC2, and their respective active association with cyclins E and A or cyclin B. HBx is also shown to override or greatly reduce serum dependence for cell cycle activation. Both HBx and serum were found to require activation of RAS to stimulate cell cycling, but only HBx could shorten checkpoint intervals. HBx therefore stimulates cell proliferation by activating RAS and a second unknown effector, which may be related to its reported ability to induce prolonged activation of JUN or to interact with cellular p53 protein. These data suggest a molecular mechanism by which HBx likely contributes to viral carcinogenesis. By deregulating checkpoint controls, HBx could participate in the selection of cells that are genetically unstable, some of which would accumulate unrepaired transforming mutations.
 ...
PMID:Hepatitis B virus HBx protein deregulates cell cycle checkpoint controls. 747 68

The HBx protein of hepatitis B virus (HBV) is a transcriptional activator that is required for infection and may play an important role in HBV-associated hepatocarcinogenesis. Recently, we and others have shown that HBx stimulates the Ras-Raf-MAP kinase cascade, which leads to enhanced cell proliferation and the activation of transcription factors AP-1 and NF-kappa B. Other studies have shown that HBx can activate transcription by interacting directly with nuclear components of the transcription machinery. Therefore we examined the basis for the different reported activities of HBx. Here, we show that HBx is a complex protein, displaying independent activities in different intracellular locations. The intracellular distribution of HBx protein was first investigated using scanning confocal laser immunomicroscopy and by genetic studies. Our work has established that HBx expressed in cultured cells is found authentically in both the cytoplasm and the nucleus. HBx is not strongly associated with any intracellular structures, but some preferential accumulation was observed near the cell surface. Next, HBx variants were constructed containing a functional or mutant nuclear localization sequence. We show that when HBx is engineered to relocate exclusively to the nucleus, it no longer activates the Ras-Raf-MAP kinase cascade, nor does it activate transcription factors AP-1 and NF-kappa B. Surprisingly, nuclear HBx fully retains the ability to stimulate HBV enhancer I, which is activated independently of the Ras and protein kinase C pathways. Therefore HBx protein stimulates signal transduction pathways in the cytoplasm and transactivates transcription elements in the nucleus. Furthermore, SV40 T antigen is shown to induce the nuclear sequestration of HBx protein and to block its activation of NF-kappa B, demonstrating that HBx is regulated by proteins that alter its intracellular distribution. The conflicting functions of HBx protein in viral infection and possibly carcinoma may involve the regulation of its differential distribution in the cell.
 ...
PMID:The hepatitis B virus HBx protein is a dual specificity cytoplasmic activator of Ras and nuclear activator of transcription factors. 758 4

Infected-cell protein 4 (ICP4) is the major transcriptional activator of herpes simplex virus (HSV) gene expression during productive infection. ICP0 has broad transactivating activity for all classes of HSV genes as well as cellular genes and genes of heterologous viruses. Together, the transactivating activities of ICP4 and ICP0 are synergistic. ICP27, which alone does not exhibit major transregulatory activity, is able to differentially activate and repress viral gene expression induced by ICP4 and ICP0. Thus, ICP27 plays a modulatory role in viral gene expression. In order to explore the functional relationships among ICP4, ICP0, and ICP27 in the regulation of viral gene expression, we have used indirect immunofluorescence to examine the intracellular localization of ICP4 in cells infected with wild-type virus or with mutant viruses that did not express functional forms of ICP0 or ICP27. Although ICP4 localized to both the nuclei and cytoplasm of cells infected with either the wild-type virus or an ICP0 null mutant virus, this protein was present exclusively in the nuclei of cells infected with an ICP27 null mutant virus, suggesting that ICP27 is able to inhibit the nuclear localization of ICP4 during virus infection. Transient expression assays with pairs of plasmids that express wild-type forms of ICP4 and ICP0 or of ICP4 and ICP27 demonstrated that ICP27 has a significant inhibitory effect on the nuclear localization of ICP4, confirming the observations made with the mutant-virus-infected cells. By using a plasmid expressing wild-type ICP4 and a series of ICP27 mutant plasmids in transient expression assays, the C-terminal half of ICP27 was shown to be required for its inhibitory effect on the nuclear localization of ICP4. In similar studies using a series of ICP4 mutant plasmids, the region of ICP4 responsive to wild-type ICP27 was mapped to the C-terminal portion of the molecule between amino acid residues 820 and 1029. The level of expression of ICP27 was shown to have a significant effect on the intracellular localization of ICP4 in transient assays. These findings are consistent with previous studies in which ICP27 was shown to have an inhibitory effect on the nuclear localization of ICP0 (Z. Zhu, W. Cai, and P. A. Schaffer J. Virol. 68:3027-3040, 1994). Thus, ICP27 has a significant inhibitory effect on the ability of the two major HSV type 1 (HSV-1) regulatory proteins to localize to the nucleus. Collectively, these findings indicate that cooperative regulation of HSV-1 gene expression may well involve intracellular compartmental constraints.
 ...
PMID:Intracellular localization of the herpes simplex virus type 1 major transcriptional regulatory protein, ICP4, is affected by ICP27. 798 45


1 2 3 4 Next >>