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)

Thyroid hormone receptors (TRs) are nuclear proteins that regulate gene expression through interactions with specific DNA sequences. It is well known that thyroid hormones have critical functions in the control of normal brain development. In the rat brain, at least three mRNA species are generated by differential processing of the TR alpha transcript. Only one of the isoforms, TR alpha-1, is a transcriptional activator, while the regulatory roles of the carboxy-terminal variants TR alpha-2 and TR alpha-2v remain unclear. In this study we have used polymerase chain reaction amplification of total RNA to compare TR alpha-1, TR alpha-2, and TR alpha-2v mRNA levels in the brainstem, cerebellum, cerebrum, midbrain, and olfactory bulbs of developing neonatal brains in rats. RNA was collected 5, 10, 15, 20, and 25 days after birth from both normal and hypothyroid animals. Coordinate expression of all three isoforms was observed in most tissues during development, with TR alpha-2 generally maintaining the highest level of expression, and TR alpha-1 the lowest. In hypothyroid tissues, TR alpha-1 message was generally increased, while TR alpha-2 was not. To explore the possible roles of the TR alpha isoforms, we have compared their DNA-binding activities. We report that compared to TR alpha-1, the carboxy-terminal variants TR alpha-2 and TR alpha-2v show different binding patterns with a thyroid hormone response element, suggesting that they bind only poorly as monomers. The varying ratios of the TR alpha isoform expression together with their distinct binding patterns and reported repressor functions suggest that TR alpha isoforms have important roles during brain development and function, and may serve to fine-tune the biological responses to thyroid hormone.
Mol Endocrinol 1991 Aug
PMID:Coordinate expression of functionally distinct thyroid hormone receptor alpha isoforms during neonatal brain development. 194 7

The virulence functions of Yersinia enterocolitica include the pYV-encoded Yop proteins and YadA adhesin as well as the chromosome-encoded enterotoxin, Yst. The yop and yadA genes form a temperature-activated regulon controlled by the transcriptional activator VirF. Gene virF, also localized on pYV, is itself thermoinduced in the absence of other pYV genes. The enterotoxin yst gene is silent in some collection strains including strain W22703. This paper describes two Tn5-Tc1 chromosomal insertion mutants of W22703 transcribing virF, and hence the yop and yadA genes, at low temperature. These mutants also resumed their production of Yst, with its typical temperature dependence. Both mutations were insertions in the same gene called ymoA for 'Yersinia modulator'. The cloned ymoA gene fully complemented the two mutations. Several properties of the mutants suggest that ymoA encodes a histone-like protein. According to the nucleic acid sequence, the product of ymoA is an 8064 Da protein rich in aspartic acid (9%), glutamic acid (9%) and lysine (10.5%), but the predicted amino acid sequence shows no similarity with any described histone-like protein. This work supports recent reports which propose a role for DNA topology and bacterial chromatin structure in thermoregulation of virulence functions.
Mol Microbiol 1991 May
PMID:ymoA, a Yersinia enterocolitica chromosomal gene modulating the expression of virulence functions. 195 83

OmpC, a major outer-membrane protein, is highly expressed when Salmonella typhi is grown in nutrient broth (NB) of either low (NB + 0% sucrose) or high (NB + 20% sucrose) osmolarity. This contrasts with the expression of Escherichia coli OmpC, which is inhibited in low osmolarity and enhanced in high osmolarity, as has been described previously (van Alphen and Lugtenberg, 1977; Verhoef et al., 1979; Kawaji et al., 1979). Nevertheless, expression of S. typhi OmpC is dependent on the E. coli OmpR transcriptional activator. These findings suggest differences between the mechanisms of osmoregulation of gene expression in both bacteria, although common effectors appear to be shared.
Mol Microbiol 1991 May
PMID:Expression of Salmonella typhi and Escherichia coli OmpC is influenced differently by medium osmolarity; dependence on Escherichia coli OmpR. 195 97

GCN4 encodes a transcriptional activator of amino acid-biosynthetic genes in Saccharomyces cerevisiae that is regulated at the translational level by upstream open reading frames (uORFs) in its mRNA leader. uORF4 (counting from the 5' end) is sufficient to repress GCN4 under nonstarvation conditions; uORF1 is required to overcome the inhibitory effect of uORF4 and stimulate GCN4 translation in amino acid-starved cells. Insertions of sequences with the potential to form secondary structure around uORF4 abolish derepression, indicating that ribosomes reach GCN4 by traversing uORF4 sequences rather than by binding internally to the GCN4 start site. By showing that wild-type regulation occurred even when uORF4 was elongated to overlap GCN4 by 130 nucleotides, we provide strong evidence that those ribosomes which translate GCN4 do so by ignoring the uORF4 AUG start codon. This conclusion is in accord with the fact that translation of a uORF4-lacZ fusion was lower in a derepressed gcd1 mutant than in a nonderepressible gcn2 strain. We also show that increasing the distance between uORF1 and uORF4 to the wild-type spacing that separates uORF1 from GCN4 specifically impaired the ability of uORF1 to derepress GCN4 translation. As expected, this alteration led to increased uORF4-lacZ translation in gcd1 cells. Our results suggest that under starvation conditions, a substantial fraction of ribosomes that translate uORF1 fail to reassemble the factors needed for reinitiation by the time they scan to uORF4, but become competent to reinitiate after scanning the additional sequences to GCN4. Under nonstarvation conditions, ribosomes would recover more rapidly from uORF1 translation, causing them all to reinitiate at uORF4 rather than at GCN4.
Mol Cell Biol 1991 Jan
PMID:Suppression of ribosomal reinitiation at upstream open reading frames in amino acid-starved cells forms the basis for GCN4 translational control. 198 42

The PUT3 gene product is a transcriptional activator required for expression of the enzymes of the proline utilization pathway. Using two methods of footprinting in vivo, we have determined that PUT3 protein is poised at the promoters of the genes encoding these enzymes and that proline-mediated induction modulates the activity of constitutively bound PUT3.
Mol Cell Biol 1991 Jan
PMID:Proline-independent binding of PUT3 transcriptional activator protein detected by footprinting in vivo. 198 47

We have cloned and sequenced a cDNA encoding gp34, a novel glycoprotein expressed in cells bearing human T-cell leukemia virus type I (HTLV-I). HTLV-I has a trans-acting transcriptional activator, p40tax, that is thought to be implicated in leukemogenesis through the activation of cellular enhancers. With a subline (JPX-9) of the human T-cell line Jurkat, in which p40tax is inducible, gp34 was shown to be of cellular origin and to be transcriptionally activated by p40tax. It was also demonstrated that two species of mRNA are generated from one copy of the gp34 gene and that these mRNAs encode the identical gp34 product and differ in the 3' untranslated region. Analysis of the deduced amino acid sequence of gp34 showed that it lacks typical signal peptides; however, it has a hydrophobic stretch for membrane anchoring and four possible N-linked glycosylation sites at the carboxy-terminal portion, indicating that it belongs to the family of membrane proteins whose carboxy-terminal portion protrudes out of the cell. The gp34 gene displayed relatively delayed induction compared with other genes activated by p40tax. Taken together with the observation of the dependence of gp34 expression on HTLV-I p40tax, unlike other p40tax-dependent genes such as those for the interleukin-2 receptor alpha chain and c-fos, which are expressed or induced under physiological conditions, we predict that the mechanism involved in the induction of gp34 expression by p40tax is distinct from and more intricate than those for the previously characterized genes.
Mol Cell Biol 1991 Mar
PMID:Molecular cloning and characterization of a novel glycoprotein, gp34, that is specifically induced by the human T-cell leukemia virus type I transactivator p40tax. 199 93

The elements regulating lens-specific expression of the mouse gamma F-crystallin gene were examined. Here we show that mouse gamma F-crystallin sequences -67 to +45 contain a low basal level of lens-specific promoter activity and that sequences -67 to -25, which are highly conserved among different gamma-crystallin genes, are able to function as a strong transcriptional activator when duplicated and placed upstream of the TATA box. We also show that nuclear factors from lens and nonlens cells are able to form different complexes with sequences centered at -46 to -36 and demonstrate that binding of the factor from lens cells correlates with lens-specific promoter activity of the mouse gamma F-crystallin gene.
Mol Cell Biol 1991 Mar
PMID:Interaction of a lens cell transcription factor with the proximal domain of the mouse gamma F-crystallin promoter. 199 7

Insulin-producing cells and fibroblasts were fused to produce hybrid lines. In hybrids derived from both hamster and rat insulinoma cells, no insulin mRNA could be detected in any of seven lines examined by Northern (RNA) analysis despite the presence in each line of the insulin genes of both parental cells. Hybrid cells were transfected with recombinant chloramphenicol acetyltransferase plasmids containing defined segments of the rat insulin I gene 5' flank. We observed no transcriptional activity of the intact insulin enhancer or of IEB2, a critical cis-acting element of the insulin enhancer. IEB2 has previously been shown to interact in vitro with IEF1, a DNA-binding activity observed selectively in insulin-producing cells. Hybrid cells showed no detectable IEF1 activity. Furthermore, the insulin enhancer was unable to reduce transcription directed by the Moloney sarcoma virus enhancer in a double-enhancer construct. Thus, extinction of insulin gene expression in the hybrids apparently does not operate through a direct action of repressors on the insulin enhancer; rather, extinction is accompanied by, and may be caused by, reduced DNA-binding activity of the putative transcriptional activator IEF1.
Mol Cell Biol 1991 Mar
PMID:Extinction of insulin gene expression in hybrids between beta cells and fibroblasts is accompanied by loss of the putative beta-cell-specific transcription factor IEF1. 199 8

The Saccharomyces cerevisiae PUT3 gene encodes a transcriptional activator that binds to DNA sequences in the promoters of the proline utilization genes and is required for the basal and induced expression of the enzymes of this pathway. The sequence of the wild-type PUT3 gene revealed the presence of one large open reading frame capable of encoding a 979-amino-acid protein. The protein contains amino-terminal basic and cysteine-rich domains homologous to the DNA-binding motifs of other yeast transcriptional activators. Adjacent to these domains is an acidic domain with a net charge of -17. A second acidic domain with a net charge of -29 is located at the carboxy terminus. The midsection of the PUT3 protein has homology to other activators including GAL4, LAC9, PPR1, and PDR1. Mutations in PUT3 causing aberrant (either constitutive or noninducible) expression of target genes in this system have been analyzed. One activator-defective and seven activator-constitutive PUT3 alleles have been retrieved from the genome and sequenced to determine the nucleotide changes responsible for the altered function of the protein. The activator-defective mutation is a single nucleotide change within codon 409, replacing glycine with aspartic acid. One activator-constitutive mutation is a nucleotide change at codon 683, substituting phenylalanine for serine. The remaining constitutive mutations resulted in amino acid substitutions or truncations of the protein within the carboxy-terminal 76 codons. Mechanisms for regulating the activation function of the PUT3 protein are discussed.
Mol Cell Biol 1991 May
PMID:Analysis of constitutive and noninducible mutations of the PUT3 transcriptional activator. 201 67

The yeast GAL4 protein, a transcriptional activator of genes involved in galactose metabolism, binds as a dimer to several closely related seventeen base pair upstream activation sequences (UASGs) that are nearly symmetric about a central dT-dA base pair. A previous study of a GAL4-UASG complex (Carey, M., Kakidani, H., Leatherwood, J., Mostashari, F. and Ptashne, M. (1989) J. Mol. Biol. 209, 423-432) elucidated a pattern of contacts consistent with the protein partially wrapping itself around the helical cylinder, assuming a B-form conformation for the DNA. Alternatively, both monomers could sit on one face of the cylinder if the DNA exists in an underwound conformation such as A-form. Spectroscopic studies that distinguish between these models are reported here. Oligonucleotides containing the consensus UASG or a nine base pair "half site" both exhibit circular dichroism (CD) spectra characteristic of B-form DNA. Two-dimensional NMR studies of the half-site also indicate a B-form conformation. When a GAL4 protein fragment containing the entire DNA-binding and dimerization domains (amino acids 1-140) is bound to the UASG, the CD spectrum above 240 nm changes only slightly, and not in a manner consistent with DNA unwinding. Our studies suggest that the UASG does not adopt an unusual underwound conformation in the absence or presence of the GAL4 protein, and favor the model in which the dimer partially wraps around the helix cylinder.
 ...
PMID:Spectroscopic studies of the DNA binding site of the GAL4 "zinc finger" protein. 201 97


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