Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0021051 (immunodeficiency)
71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have asked how the human cytomegalovirus major immediate-early 1 (IE1) and 2 (IE2) proteins act to transactivate heterologous cellular and viral promoters. Here we show that transactivation of the human immunodeficiency virus long terminal repeat and the 70,000-molecular-weight heat shock protein (hsp70) promoter by IE1 is TATA box independent and that the IE1 protein does not interact directly with the TATA box-binding factor TFIID. Conversely, transactivation of these promoters by IE2 is TATA box dependent and a direct interaction between IE2 and TFIID occurs, suggesting that IE2 transactivation is mediated through interaction with TFIID.
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PMID:The human cytomegalovirus 80-kilodalton but not the 72-kilodalton immediate-early protein transactivates heterologous promoters in a TATA box-dependent mechanism and interacts directly with TFIID. 131 14

A critical regulatory element in many promoters transcribed by RNA polymerase II is the "TATA" box, which is located 25-30 nucleotides upstream of the transcription initiation site. TFIID is a biochemically defined HeLa cell nuclear fraction containing a transcription factor activity that binds specifically to the TATA box and is critical in determining both basal and regulated promoter activity. Recently, the gene for a TATA-binding protein was cloned and found to bind to various TATA elements and to substitute for TFIID in stimulating basal gene expression in in vitro transcription systems. However, it is possible that additional cellular factors can bind to the TATA element and influence the level of gene expression. By using lambda gt11 expression cloning with oligonucleotides corresponding to the human immunodeficiency virus 1 TATA element, we report the identification of a cellular protein with a calculated molecular mass of 123 kDa that we designate TATA element modulatory factor (TMF). TMF binds to the human immunodeficiency virus 1 TATA element in gel-retardation assays and inhibits activation of the viral long terminal repeat by the TATA-binding protein in in vitro transcription assays. TMF contains leucine-zipper amino acid motifs and exhibits homology in its DNA binding domain with the phage-encoded DNA binding protein Ner. Chromosomal mapping localizes the TMF gene to human chromosome 3p12-p21, which is a site of frequent rearrangements in lung and renal carcinomas. Thus, TMF is a transcription factor that likely regulates the expression of both viral and cellular genes.
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PMID:Cloning and chromosomal mapping of a human immunodeficiency virus 1 "TATA" element modulatory factor. 140 43

A cellular DNA binding protein, LBP-1, sequentially interacts in a concentration-dependent manner with two sites that surround the transcriptional initiation site of the human immunodeficiency virus type 1 (HIV-1) promoter. Although sequences in the downstream site (site I) were found to enhance transcription, purified LBP-1 specifically repressed transcription in vitro by binding to the upstream site (site II), which overlaps the TATA element. The binding of human TATA binding factor (TFIID) to the promoter before LBP-1 blocked repression, suggesting that repression resulted from an inhibition of TFIID binding to the TATA element. Furthermore, mutations that eliminated binding to site II both prevented repression in vitro and increased HIV-1 transcription in stably transformed cells. These findings suggest that a cellular factor regulates HIV-1 transcription in a manner that is characteristic of bacterial repressors and that this factor could be important in HIV-1 latency.
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PMID:Repression of HIV-1 transcription by a cellular protein. 200 21

The TATA box-binding transcription factor TFIID from Saccharomyces cerevisiae was tested for its ability to mediate regulatory factor functions both in a cell-free system reconstituted with other general initiation factors (purified from HeLa cells) and in a combined nucleosome assembly-transcription system. In the latter assay recombinant yeast TFIID, expressed in and purified from bacteria, was sufficient to prevent nucleosome assembly-mediated repression and to mediate transcriptional enhancement of the adenovirus major late promoter by the gene-specific activator USF. In contrast, recombinant yeast TFIID was unable to mediate activation by USF in the system reconstituted only with purified general factors. Under the same conditions a partially purified natural yeast TFIID was able to mediate activation by both USF and Sp1 (assayed with the human immunodeficiency virus promoter), but to a lesser extent than observed with a partially purified natural human TFIID. The implications of these findings are discussed with respect to the structure of the yeast and human TATA factors and the possible involvement either of specific TFIID modifications or of coactivators.
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PMID:Recombinant yeast TFIID, a general transcription factor, mediates activation by the gene-specific factor USF in a chromatin assembly assay. 225 Dec 56

Expression of human immunodeficiency virus type 1 (HIV-1) genes is regulated by the trans activator Tat. Tat exerts its effects by increasing the rate of transcription, but the mechanism by which it does so is still unknown. To study the cellular factors required for Tat trans activation, we have expressed functional Gst-Tat fusion protein and used it to construct affinity columns. Our findings are as follows. (i) A Gst-Tat affinity matrix depleted HeLa nuclear extracts of a factor(s) required for Tat function. A Tat mutant bearing the missense mutation lysine to alanine at position 41 was incapable of this depletion. (ii) Tat trans activation was recovered by addition of unfractionated nuclear extract, the 0.5 M KCl elution fraction from the Tat affinity column, or sedimentation gradient fractions of HeLa extracts. The activity from the gradients sedimented with an apparent molecular mass of 200 kDa. (iii) Tat trans activation could not be recovered by use of recombinant human TATA-binding protein or partially purified TFIID. (iv) trans activation by Tat was blocked by heating of the nuclear extract under conditions in which basal transcription was not decreased. Our data demonstrate for the first time the existence of unique Tat coactivators distinct from factors required for general basal transcription.
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PMID:Transcriptional trans activation by human immunodeficiency virus type 1 Tat requires specific coactivators that are not basal factors. 770 38

TFIID is a multisubunit protein complex comprised of the TATA-binding protein (TBP) and multiple TBP-associated factors (TAFs). The TAFs in TFIID are essential for activator-dependent transcription. The cloning of a complementary DNA encoding a human TFIID TAF, TAFII55, that has no known homolog in Drosophila TFIID is now described. TAFII55 is shown to interact with the largest subunit (TAFII230) of human TFIID through its central region and with multiple activators--including Sp1, YY1, USF, CTF, adenoviral E1A, and human immunodeficiency virus-type 1 Tat proteins--through a distinct amino-terminal domain. The TAFII55-interacting region of Sp1 was localized to its DNA-binding domain, which is distinct from the glutamine-rich activation domains previously shown to interact with Drosophila TAFII110. Thus, this human TFIID TAF may be a co-activator that mediates a response to multiple activators through a distinct mechanism.
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PMID:Cloning of an intrinsic human TFIID subunit that interacts with multiple transcriptional activators. 782 54

Tat regulation of human immunodeficiency virus (HIV) transcription is unique because of its specificity for an RNA target, TAR, and its ability to increase the efficiency of elongation by polymerase. A reconstituted reaction that is Tat-specific and TAR-dependent for activation of HIV transcription has been used to identify and partially purify a cellular activity that is required for trans-activation by Tat, but not by other activators. In the reaction, Tat stimulates the efficiency of elongation by polymerase, whereas Sp1 and other DNA sequence-specific transcription factors activate the rate of initiation. Furthermore, while TATA binding protein (TBP)-associated factors (TAFs) in the TFIID complex are required for activation by transcription factors, they are dispensable for Tat function. Thus, Tat acts through a novel mechanism, which is mediated by a specific host cellular factor, to stimulate HIV-1 gene expression.
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PMID:Novel mechanism and factor for regulation by HIV-1 Tat. 783 43

LBP-1 is a cellular protein which binds strongly to sequences around the human immunodeficiency virus type 1 (HIV-1) initiation site and weakly over the TATA box. We have previously shown that LBP-1 represses HIV-1 transcription by inhibiting the binding of TFIID to the TATA box. Four similar but distinct cDNAs encoding LBP-1 (LBP-1a, -b, -c, and -d) have been isolated. These are products of two related genes, and each gene encodes two alternatively spliced products. Comparison of the amino acid sequence of LBP-1 with entries in the available protein data bases revealed the identity of LBP-1c to alpha-CP2, an alpha-globin transcription factor. These proteins are also homologous to Drosophila melanogaster Elf-1/NTF-1, an essential transcriptional activator that functions during Drosophila embryogenesis. Three of the recombinant LBP-1 isoforms show DNA binding specificity identical to that of native LBP-1 and bind DNA as a multimer. In addition, antisera raised against recombinant LBP-1 recognize native LBP-1 from HeLa nuclear extract. Functional analyses in a cell-free transcription system demonstrate that recombinant LBP-1 specifically represses transcription from a wild-type HIV-1 template but not from an LBP-1 mutant template. Moreover, LBP-1 can function as an activator both in vivo and in vitro, depending on the promoter context. Interestingly, one isoform of LBP-1 which is missing the region of the Elf-1/NTF-1 homology is unable to bind DNA itself and, presumably through heteromer formation, inhibits binding of the other forms of LBP-1, suggesting that it may function as a dominant negative regulator.
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PMID:Characterization of a family of related cellular transcription factors which can modulate human immunodeficiency virus type 1 transcription in vitro. 811 10

The tat gene of the human immunodeficiency virus (HIV) plays a central role in the activation and life cycle of HIV. The tat protein (Tat) specifically transactivates HIV transcription in vivo and in vitro, exerting its effects at the level of transcriptional initiation and elongation. Here we report that Tat binds directly to the basal transcription factor TFIID. The transcriptional activity of HeLa extracts was depleted after chromatography on a Tat affinity column, which specifically retained the polymerase II-specific factor TFIID. Direct interaction of Tat with holo-TFIID, composed of TATA-binding protein (TBP) and associated factors (TAFs), was observed. Tat binds, through amino acids 36-50, directly to the TBP subunit of TFIID. Our results suggest that Tat may transduce upstream or downstream regulatory signals by direct interaction with the basal transcription factor TFIID.
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PMID:Direct interaction of human TFIID with the HIV-1 transactivator tat. 812 96

Second-site revertants from replication-incompetent molecular clones of human immunodeficiency virus (HIV) contain base substitutions adjacent to the TATA motif. The altered TATA box motifs were analyzed for their effect(s) on virus infectivity, long terminal repeat (LTR)-directed expression in transient transfection assays, in vitro RNA synthesis, and assembly of the TFIID-TFIIA preinitiation complex. The revertant TATA boxes accelerated the kinetics of HIV replication when present in the context of an LTR containing a Sp1 mutation (deletion or site specific); no effect was observed on the infectivity of wild-type HIV. In chloramphenicol acetyltransferase assays and in vitro transcription systems, the altered TATA box motifs led to elevated basal levels of RNA synthesis from NF-kappa B- and Sp1-mutagenized and wild-type templates, respectively, but did not increase responsiveness to Tat transactivation. The revertant TATA boxes accelerated the binding of TFIID and TFIIA to the LTR and stabilized their association with the promoter. The revertants did not assemble a more-processive elongation complex. These results suggest that in the context of an impaired enhancer/promoter (viz., three mutated Sp1 elements), a series of HIV revertants emerge which contain LTR alterations that significantly augment basal RNA synthesis. The TATA motif revertants are capable of rescuing the enhancer/promoter defect and sustain virus infectivity.
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PMID:Second-site long terminal repeat (LTR) revertants of replication-defective human immunodeficiency virus: effects of revertant TATA box motifs on virus infectivity, LTR-directed expression, in vitro RNA synthesis, and binding of basal transcription factors TFIID and TFIIA. 815 90


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