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 cellular proto-oncogene c-myc is involved in cell proliferation and transformation but is also implicated in the induction of programmed cell death (apoptosis). The c-Myc protein is a transcriptional activator with a carboxyl-terminal basic region/helix-loop-helix (HLH)/leucine zipper (LZ) domain. It forms heterodimers with the HLH/LZ protein Max and transactivates gene expression after binding DNA E-box elements. We have studied the phenotype of dominant-negative mutants of c-Myc and Max in microinjection experiments. Max mutants with a deleted or mutated basic region inhibited DNA synthesis in serum-stimulated 3T3-L1 mouse fibroblasts. In contrast, mutants of c-Myc expressing only the basic region/HLH/LZ or HLH/LZ domains rapidly induced apoptosis at low and high serum levels. Co-expression of the HLH/LZ domains of c-Myc and Max failed to do so. We suggest that the c-Myc HLH/LZ domain induces apoptosis by specific interaction with cellular factors different to Max.
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PMID:Induction of apoptosis by the c-Myc helix-loop-helix/leucine zipper domain in mouse 3T3-L1 fibroblasts. 749 3

The sulfur regulatory system of Neurospora crassa is composed of a set of structural genes involved in sulfur catabolism controlled by a genetically defined set of trans-acting regulatory genes. These sulfur regulatory genes include cys-3+, which encodes a basic region-leucine zipper transcriptional activator, and the negative regulatory gene scon-2+. We report here that the scon-2+ gene encodes a polypeptide of 650 amino acids belonging to the expanding beta-transducin family of eukaryotic regulatory proteins. Specifically, SCON2 protein contains six repeated G beta-homologous domains spanning the C-terminal half of the protein. SCON2 represents the initial filamentous fungal protein identified in the beta-transducin group. Additionally, SCON2 exhibits a specific amino-terminal domain that potentially defines another subfamily of beta-transducin homologs. Expression of the scon-2+ gene has been examined using RNA hybridization and gel mobility-shift analysis. The dependence of scon-2+ expression on CYS3 function and the binding of CYS3 to the scon-2+ promoter indicate the presence of an important control loop within the N. crassa sulfur regulatory circuit involving CYS3 activation of scon-2+ expression. On the basis of the presence of beta-transducin repeats, the crucial role of SCON2 in the signal-response pathway triggered by sulfur limitation may be mediated by protein-protein interactions.
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PMID:The sulfur controller-2 negative regulatory gene of Neurospora crassa encodes a protein with beta-transducin repeats. 772 64

We have screened a cDNA library prepared from tomato (Lycopersicon esculentum Mill. cv. VFNT Cherry) shoot tips for homeobox-containing clones. The isolated cDNA clone THOM1 (tomato homeobox gene 1) contains a homeobox, a leucine zipper motif and and an acidic region. These features support the hypothesis that the THOM1 gene product acts as a transcriptional activator. THOM1 is highly expressed in the vegetative shoot apical meristem, the floral meristem and axillary meristems. Young derivatives of these meristems show similar levels of THOM1 transcripts which decrease with increasing age of the respective tissue. The THOM1 gene is located in the centromere region of chromosome 1 and belongs to a small gene family of the tomato genome.
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PMID:Isolation and characterization of the tomato homeobox gene THOM1. 776 50

A 33 membered polypeptide corresponding to the leucine zipper region of the yeast transcriptional activator GCN4 was synthesized by solid phase chemical synthesis and characterized. Asparagine in the hydrophobic core of the molecule is replaced by valine in the synthetic variant. The correctness of amino acid sequence of the preparation is corroborated by direct sequencing. High-speed equilibrium ultracentrifugation, ultraviolet circular dichroism spectroscopy and scanning microcalorimetry have been employed to demonstrate that in solution the peptide forms a highly stable triple-stranded alpha-helical coiled coil. The stability of the mutant form is 40 degrees C higher than the dimeric form of natural peptide under similar conditions. It was proposed that location of some polar groups in the 'a' and 'd' positions of natural two-stranded coiled coils may be regarded as protection against alternative triple- and multistranded conformations.
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PMID:Synthesis and properties of the peptide corresponding to the mutant form of the leucine zipper of the transcriptional activator GCN4 from yeast. 783 Dec 80

One of the first oncogenes identified from human tumors was c-myc, which is frequently activated in Burkitt's lymphomas due to chromosomal translocations. Subsequently, members of the myc oncogene family were found to be amplified in neuroblastoma and small-cell lung cancer. In normal cells, Myc activity has been shown to be both necessary and sufficient for resting cells to enter the cell cycle. Interestingly, it appears that Myc not only drives the cell cycle, but also induces cell death by apoptosis in certain situations. Myc contains a transcriptional activation domain and a basic helix-loop-helix-leucine zipper DNA-binding and dimerization domain. As a heterodimer with a structurally related protein, Max, Myc can bind DNA in a sequence-specific manner. These results suggest that the Myc/Max heterodimer functions as a transcriptional activator of genes that are critical for the regulation of cell growth.
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PMID:Myc protein: partners and antagonists. 794 8

Expression of c-myc with constitutively active mutants of the ras gene results in the cooperative transformation of primary fibroblasts, although the precise mechanism by which these genes cooperate is unknown. Since c-Myc has been shown to function as a transcriptional activator, we have examined the ability of c-Myc and activated Ras (H-RasV-12) to cooperatively induce the promoter activity of cdc2, a gene which is critical for cell cycle progression. Microinjection of expression constructs encoding H-RasV-12 and c-Myc along with a cdc2 promoter-luciferase reporter plasmid into quiescent cells led to an increase in cdc2 promoter activity approximately 30 h after injection, a period which coincides with the S-to-G2/M transition in these cells. Expression of H-RasV-12 alone weakly activated the cdc2 promoter, while expression of c-Myc alone had no effect. Mutants of c-Myc lacking either the leucine zipper dimerization domain or the phosphoacceptor site Ser-62 could not cooperate with H-RasV-12 to induce the cdc2 promoter. These mutants also lacked the ability to cooperate with H-RasV-12 to stimulate DNA synthesis. Deletion analysis identified a distinct region of the cdc2 promoter which was required for c-Myc responsiveness. Taken together, these observations suggest a mechanistic link between the molecular activities of c-Myc and Ras and induction of the cell cycle regulator Cdc2.
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PMID:c-Myc cooperates with activated Ras to induce the cdc2 promoter. 806 6

The t(17;19) translocation in acute lymphoblastic leukemias results in creation of E2A-hepatic leukemia factor (HLF) chimeric proteins that contain the DNA-binding and protein dimerization domains of the basic leucine zipper (bZIP) protein HLF fused to a portion of E2A proteins with transcriptional activation properties. An in vitro binding site selection procedure was used to determine DNA sequences preferentially bound by wild-type HLF and chimeric E2A-HLF proteins isolated from various t(17;19)-bearing leukemias. All were found to selectively bind the consensus sequence 5'-GTTACGTAAT-3' with high affinity. Wild-type and chimeric HLF proteins also bound closely related sites identified previously for bZIP proteins of both the proline- and acidic amino acid-rich (PAR) and C/EBP subfamilies; however, E2A-HLF proteins were significantly less tolerant of certain deviations from the HLF consensus binding site. These differences were directly attributable to loss of an HLF ancillary DNA-binding domain in all E2A-HLF chimeras and were further exacerbated by a zipper mutation in one isolate. Both wild-type and chimeric HLF proteins displayed transcriptional activator properties in lymphoid and nonlymphoid cells on reporter genes containing HLF or C/EBP consensus binding sites. But on reporter genes with nonoptimal binding sites, their transcriptional properties diverged and E2A-HLF competitively inhibited activation by wild-type PAR proteins. These findings establish a spectrum of binding site-specific transcriptional properties for E2A-HLF which may preferentially activate expression of select subordinate genes as a homodimer and potentially antagonize expression of others through heteromeric interactions.
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PMID:DNA-binding and transcriptional regulatory properties of hepatic leukemia factor (HLF) and the t(17;19) acute lymphoblastic leukemia chimera E2A-HLF. 806 31

The Opaque 2 (O2) gene encodes a transcriptional activator of the basic region/leucine zipper family, which controls the synthesis of a major storage protein class in maize endosperm, the 22 kDa alpha-zeins, and of several other non-zein polypeptides including b32. We demonstrate, by analysing O2 mRNAs in different organs of maize plants, that the O2 gene is only active in the endosperm. Its transcription is precisely controlled during seed development: O2 mRNAs are first detected 10 days after pollination and accumulate in the endosperm over a period of 20 days. When introduced into tobacco plants, the O2 promoter directs the expression of the beta-glucuronidase (GUS) reporter gene in endosperm, but also in the embryo, cotyledons and pollen. The first 185 bp of the O2 promoter is sufficient for developmentally regulated expression in tobacco seeds. A distinct cis-acting element, located between positions -185 and -520, directs expression in the cotyledons of tobacco seedlings. The possible origins of this breakdown in promoter specificity in the heterologous host are discussed.
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PMID:Differences in cell type-specific expression of the gene Opaque 2 in maize and transgenic tobacco. 807 65

Heat shock factor (HSF), the transcriptional activator of eukaryotic heat shock genes, is induced to bind DNA by a monomer to trimer transition involving leucine zipper interactions. Although this mode of regulation is shared among many eukaryotic species, there is variation in the temperature at which HSF binding activity is induced. We investigated the basis of this variation by analysing the response of a human HSF expressed in Drosophila cells and Drosophila HSF expressed in human cells. We report here that the temperature that induces DNA binding and trimerization of human HSF in Drosophila was decreased by approximately 10 degrees C to the induction temperature for the host cell, whereas Drosophila HSF expressed in human cells was constitutively active. The results indicate that the activity of HSF in vivo is not a simple function of the absolute environmental temperature.
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PMID:Induction temperature of human heat shock factor is reprogrammed in a Drosophila cell environment. 832 22

DNA-binding proteins containing the basic helix-loop-helix (bHLH) domain have been implicated in lineage determination and the regulation of specific gene expression in a number of cell types. By oligonucleotide screening of an adipocyte cDNA expression library, we have identified a novel member of the bHLH-leucine zipper transcription factor family designated ADD1. ADD1 mRNA is expressed predominantly in brown adipose tissue in vivo and is regulated during both determination and differentiation of cultured adipocyte cell lines. ADD1 can function as a sequence-specific transcriptional activator in that it stimulates expression of a chloramphenicol acetyltransferase vector containing multiple ADD1 binding sequences but is unable to activate the myosin light-chain enhancer, which contains multiple binding sites for another bHLH factor, MyoD. ADD1 can also activate transcription through a binding site present in the 5'-flanking region of the fatty acid synthetase gene which is expressed in a differentiation-dependent manner in adipose cells. These data suggest that ADD1 plays a role in the regulation of determination- and differentiation-specific gene expression in adipocytes.
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PMID:ADD1: a novel helix-loop-helix transcription factor associated with adipocyte determination and differentiation. 833 13


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