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)

Inducible gene expression in eukaryotes is mainly controlled by the activity of transcriptional activator proteins, such as NF-kappa B (refs 1-3), a factor activated upon treatment of cells with phorbol esters, lipopolysaccharide, interleukin-1 and tumour necrosis factor-alpha. Activation of NF-kappa B involves release of the inhibitory subunit I kappa B from a cytoplasmic complex with the DNA-binding subunits Rel-A (formerly p65) and p50 (refs 6, 7). Cell-free experiments have suggested that protein kinase C and other kinases transfer phosphoryl groups onto I kappa B causing release of I kappa B and subsequent activation of NF-kappa B. Here we report that I kappa B-alpha (formerly MAD-3) is degraded in cells after stimulation with phorbol ester, interleukin-1, lipopolysaccharide and tumour necrosis factor-alpha, an event coincident with the appearance of active NF-kappa B. Treatment of cells with various protease inhibitors or an antioxidant completely prevented the inducible decay of I kappa B-alpha as well as the activation of NF-kappa B. Our findings suggest that the activation of NF-kappa B relies on an inducible degradation of I kappa B-alpha through a cytoplasmic, chymotrypsin-like protease. In intact cells, phosphorylation of I kappa B-alpha is apparently not sufficient for activation of NF-kappa B.
Nature 1993 Sep 09
PMID:Rapid proteolysis of I kappa B-alpha is necessary for activation of transcription factor NF-kappa B. 837 61

The X-ray structure of the DNA binding domain of the yeast transcriptional activator protein GCN4 bound to a DNA fragment containing the sequence of the perfectly symmetrical ATF/CREB site has been solved to 3.0 A resolution. The architecture of this specific recognition complex supports the current model for bZIP proteins: a homodimer of parallel alpha-helices form an interhelix coiled-coil region via the leucine zipper, and the two N-terminal basic regions fit into the major groove of half sites on opposite sides of the DNA double helix. The structure shows that DNA flexibility plays the predominant role in the preservation of protein contacts with the symmetric ATF/CREB site (ATGACGTCAT) as compared to the pseudo-symmetric AP-1 target site (ATGACTCAT), overcoming the positional displacement of functional groups introduced by the additional G.C base-pair at the center of the ATF/CREB sequence.
J Mol Biol 1993 Sep 05
PMID:The X-ray structure of the GCN4-bZIP bound to ATF/CREB site DNA shows the complex depends on DNA flexibility. 837 81

Cooperative DNA binding of the bovine papillomavirus type 1 (BPV-1) E2 transcriptional activator (E2-TA) is thought to play a role in the transcriptional synergism of multiple E2-responsive DNA elements (J. Ham, N. Dostatni, J.-M. Gauthier, and M. Yaniv, Trends Biochem. Sci. 16:440-444, 1991). Binding-equilibrium considerations show that such involvement is unlikely, thereby suggesting that the E2-TA cooperative capacity may have evolved to play other, different roles. The role of cooperative interactions in the antagonistic activity of BPV-1-positive and BPV-1-negative E2 regulatory proteins was investigated by an in vitro quantitative gel shift assay. Viral repressor E2-TR, a truncated peptide encompassing the activator DNA-binding domain, possesses a small but measurable cooperative capacity. Furthermore, the minimal E2 DNA-binding domain interacts with the activator in a positive, heterocooperative manner. As a result, the in vitro competition of full-length and truncated E2 peptides appears to be (macroscopically) noncooperative. This heterocooperative effect is probably dominant in latently infected G0-G1 cells, in which repressor E2-TR is 10- to 20-fold more abundant than the activator. The data are discussed considering the possible role of homo- and heterocooperative DNA binding in E2-conditional gene expression.
J Virol 1993 Sep
PMID:Cooperative DNA binding of the bovine papillomavirus E2 transcriptional activator is antagonized by truncated E2 polypeptides. 839 66

Pseudomonas aeruginosa K372 is deficient in the production of both the 75-kDa ferripyochelin receptor protein and pyochelin. A 1.8-kb EcoRI-SalI fragment which restored production of both the receptor protein and pyochelin was cloned. Nucleotide sequencing of the fragment revealed an open reading frame of 888 bp, designated pchR (pyochelin), capable of encoding a 296-amino-acid protein of a 32,339-Da molecular mass. By using a phage T7-based expression system, a protein of ca. 32 kDa was produced off the 1.8-kb fragment, confirming that this open reading frame was indeed expressed. A region exhibiting homology to the consensus Fur-binding site of Escherichia coli was identified upstream of the pchR coding region overlapping a putative promoter. In addition, the C-terminal 80 amino acid residues of PchR showed approximately 50% homology (identity, 31%; conserved changes, 19%) to the carboxy terminus of AraC, a known transcriptional activator of gene expression in E. coli, Salmonella typhimurium, Citrobacter freundii, and Erwinia chrysanthemi. Within the C-terminal region of PchR, AraC, and a number of other members of the AraC family of transcriptional activators, there exists a highly conserved 17-residue domain where, in fact, two residues are strictly maintained and two others exhibit only conserved changes, suggesting a common functional significance to this region in all of these proteins. These data are consistent with a role for PchR as a transcriptional activator of pyochelin and ferripyochelin receptor synthesis in P. aeruginosa. In agreement with this, a PchR mutant obtained by in vitro mutagenesis and gene replacement was deficient in production of the ferripyochelin receptor and pyochelin.
J Bacteriol 1993 Sep
PMID:Cloning and sequence analysis of a gene (pchR) encoding an AraC family activator of pyochelin and ferripyochelin receptor synthesis in Pseudomonas aeruginosa. 839 86

Proliferation and differentiation of B lymphocytes are usually concurrent but independently regulated events. Anti-mu treatment of murine B lymphocytes stimulated with LPS provides a model system in which proliferation and differentiation may be independently studied. This treatment causes enhanced proliferation but with coordinate suppression of transcription of a family of unrelated genes including those for Ig heavy and light chains, J chain, and endogenous murine leukemia virus (MuLV) sequences. We show that in comparison to B lymphocytes stimulated with LPS alone cells stimulated with a combination of anti-mu and LPS exhibit relatively increased amounts of a nuclear binding factor(s), NF mu E1, which interacts with the B (mu E1) site of the IgH enhancer; binding is strongly inhibited by a synthetic probe of the B sequence. A negative regulatory sequence contained within the upstream conserved region (UCR) of the MuLV long terminal repeat (LTR) is identical to the complement of mu E1 in eight of nine bases and inhibits binding of NF mu E1 to the IgH enhancer probe. The mu E1 site is also present 3' to the kappa-light chain gene; binding of this sequence to a repressor protein may coordinately suppress the transcription of mu, kappa, and MuLV genes. Others have reported that the cDNA encoding NF mu E1, also known as mu EBP-B, CF-1, and YY-1, predicts a protein with structural features consistent with variable function as either a transcriptional activator or repressor.
J Immunol 1993 Sep 15
PMID:Coordinate transcriptional control of murine endogenous retrovirus and Ig genes during B cell differentiation. 839 53

Nuclear respiratory factor 1 (nrf-1) is a transcriptional activator that is most probably essential in the regulation of mitochondrial biogenesis. In studies of the expression of the NRF-1 gene in cultured human fibroblasts, using RT-PCR, we identified two distinct transcripts, one of which contained an in-frame deletion of 198 bp. Analysis of genomic DNA by sequencing, showed that the shorter mRNA is the result of alternative splicing (exon skipping). The shorter transcript will result in an isoform of the protein that lacks the carboxy-terminal part of the DNA binding domain, which might influence transcriptional activation by normal nrf-1. The alternatively spliced transcript was also present in other human cell lines and in several human tissues. A quantitative PCR analysis showed that the percentages of the alternatively spliced transcript ranged from 3 to 17%. Differences in the percentage of alternatively spliced NRF-1 pre-mRNA may influence mitochondrial biogenesis under variable physiological conditions and could play a role in distinct mitochondrial diseases.
Hum Mol Genet 1995 Sep
PMID:The pre-mRNA of nuclear respiratory factor 1, a regulator of mitochondrial biogenesis, is alternatively spliced in human tissues and cell lines. 854 44

The phenomenon of cell-density-dependent control of gene expression, called autoinduction, has long been a subject of interest and investigation in bioluminescent marine bacteria. It is now becoming clear that many other bacteria, including animal and plant pathogens, use an autoinduction mechanism to regulate a variety of functions. Cell-density-dependent gene expression provides an excellent example of multicellular behaviour in the prokaryotic kingdom where a single cell is able to communicate and sense when a minimal population unit, a 'quorum' of bacteria, is achieved in order for certain behaviour of the population to be performed efficiently. Regulation of bacterial bioluminescence has been studied for many years and represents the best model system for understanding the mechanism of cell-density-dependent gene expression. This review will focus on transcriptional regulation of the Vibrio fischeri luminescence genes emphasizing the role of the transcriptional activator LuxR and possible autoinduction mechanisms that occur in E. coli. Alternative views and opinions regarding the molecular details of the autoinduction mechanism will be discussed.
Mol Microbiol 1995 Sep
PMID:Transcriptional regulation of bioluminesence genes from Vibrio fischeri. 859 30

A yeast protein has been identified that stimulates basal transcription by RNA polymerase II, binds both single- and double-stranded DNA, and interacts with both a general transcription factor and a transcriptional activator. Phosphorylation appears to regulate these interactions. The gene for the transcriptional stimulatory protein, termed TSP1, was cloned and found to be dispensable for yeast cell viability. The deduced amino acid sequence is similar to that of mammalian coactivator protein PC4.
J Biol Chem 1996 Sep 06
PMID:A yeast transcriptional stimulatory protein similar to human PC4. 870 84

In phototrophic and chemoautotrophic proteobacteria, genes encoding enzymes of the Calvin-Benson-Bassham pathway of CO2 fixation are often found in clusters that are transcribed from a single promoter under control of the LysR-type transcriptional activator, CbbR. Mutations affecting CbbR prevent induction of cbb genes. Gel-retardation assays have demonstrated CbbR binding to putative regulatory regions of cbb operons, and in two cases, footprinting experiments have delimited the nucleotide sequence protected by CbbR. Fusion of cbb control sequences to reporter genes has allowed the regions required for promoter activity to be defined, and recent experiments indicate that the cbb regulon in Rhodobacter is controlled by a global two-component signal transduction system that also regulates other metabolic processes in this organism. Different ways of regulating CBB cycle enzymes that also have roles in heterotrophic metabolism have recently been discovered. In cyanobacteria, the genes of the CBB pathway are organized and regulated differently, and these oxygen-evolving phototrophic bacteria have evolved different strategies to control the assimilation of CO2.
Arch Microbiol 1996 Sep
PMID:The molecular regulation of the reductive pentose phosphate pathway in Proteobacteria and Cyanobacteria. 870 90

The Tax protein of human T-cell lymphotropic virus type 1 (HTLV-1) is a 40-kDa transcriptional activator which is critical for HTLV-1 gene regulation and virus-induced cellular transformation. Tax is localized to the DNA through its interaction with the site-specific activators cyclic AMP-responsive element-binding protein, NF-kappaB, and serum response factor. It has been suggested that the recruitment of Tax to the DNA positions Tax for interaction with the basal transcriptional machinery. On the basis of several independent assays, we now report a physical and functional interaction between Tax and the transcription factor, TFIIA. First, Tax was found to interact with the 35-kDa (alpha) subunit of TFIIA in the yeast two-hybrid interaction system. Importantly, two previously characterized mutants with point mutations in Tax, M32 (Y196A, K197S) and M41 (H287A, P288S), which were shown to be defective in Tax-activated transcription were unable to interact with TFIIA in this assay. Second, a glutathione-S-transferase (GST) affinity-binding assay showed that the interaction of holo-TFIIA with GST-Tax was 20-fold higher than that observed with either the GST-Tax M32 activation mutant or the GST control. Third, a coimmunoprecipitation assay showed that in HTLV-1-infected human T lymphocytes, Tax and TFIIA were associated. Finally, TFIIA facilitates Tax transactivation in vitro and in vivo. In vitro transcription studies showed reduced levels of Tax-activated transcription in cell extracts depleted of TFIIA. In addition, transfection of human T lymphocytes with TFIIA expression vectors enhanced Tax-activated transcription of an HTLV-1 long terminal repeat-chloramphenicol acetyltransferase reporter construct. Our study suggests that the interaction of Tax with the transcription factor TFIIA may play a role in Tax-mediated transcriptional activation.
Mol Cell Biol 1996 Sep
PMID:Interaction of the human T-cell lymphotropic virus type 1 tax transactivator with transcription factor IIA. 875 22


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