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)

We describe the activities of a wide array of deletion mutants of GAL4, a yeast transcriptional activator. We identify two short regions of GAL4, each of which activates transcription when fused to the DNA-binding region of the molecule. Very large portions of GAL4 are not required for gene activation.
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PMID:Deletion analysis of GAL4 defines two transcriptional activating segments. 302 47

The ada gene of Escherichia coli K-12 encodes the regulatory protein for the adaptive response to alkylating agents. A set of plasmids carrying ordered deletions from the 3' end of the ada gene were isolated and characterized. These ada deletions encode fusion proteins that derive their amino termini from ada and their carboxyl termini from the downstream vector sequence that occurs before an in-frame stop codon. Several of these ada deletions encode Ada derivatives that constitutively activate ada transcription to very high levels. A second class of ada deletions encode Ada derivatives that are dominant inhibitors of the inducible transcription of ada but are inducible activators of alkA transcription. In addition, we found that two Ada derivatives containing the same ada sequences but fused to different vector-derived tails have strikingly different properties. One Ada derivative constitutively activates both ada and alkA expression to very high levels. In contrast, the other Ada derivative is an inducible activator of ada expression, like the wild-type Ada protein, but is not an inducible activator of alkA transcription. Our data suggest that the carboxyl terminus of the Ada protein plays a key role in modulating the ability of the Ada protein to function as a transcriptional activator.
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PMID:Alteration of the carboxyl-terminal domain of Ada protein influences its inducibility, specificity, and strength as a transcriptional activator. 314 84

The toxR gene encodes a transcriptional activator controlling cholera toxin, pilus, and outer-membrane protein expression in V. cholerae. Nucleotide sequence and mutational analysis has identified the toxR gene product as a 32,527 dalton protein. Hydropathicity analysis of the derived amino acid sequence of ToxR predicts a transmembrane structure. The properties of hybrid proteins composed of N-terminal fragments of ToxR fused to the periplasmic enzyme alkaline phosphatase provide additional evidence for the transmembrane topology of the ToxR protein. These fusion proteins also allowed the localization of the transcriptional activation and DNA binding domains of the ToxR protein to its cytoplasmically located N-terminal portion. DNA binding assays and a deletion analysis of the cholera toxin promoter support a model for transcriptional activation that involves ToxR binding to a tandemly repeated 7 bp DNA sequence 56 bp upstream of the transcriptional start point.
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PMID:Cholera toxin transcriptional activator toxR is a transmembrane DNA binding protein. 380 95

The GATA motif (WGATAR) is found in the promoter regions of numerous Caenorhabditis elegans genes, including two intestine-specific genes, vit-2 and ges-1, in which it has been shown to be required for promoter function. The protein ELT-1, encoded by a single-copy gene homologous to the GATA family of vertebrate transcription factors, is potentially capable of interacting with this element. In order to determine whether ELT-1 is a transcriptional activator that recognizes this sequence, we have expressed it under the control of the GAL1 promoter in yeast. lacZ driven by the CYC1 promoter lacking an upstream activation sequence (UAS) but containing GATA sequences was used as a reporter. beta-Galactosidase was expressed upon induction only when GATA sequences were present, and expression was increased dramatically by additional binding sites. Deletion analysis demonstrated that the C terminus, containing only one of the two zinc fingers, is sufficient for activation. In addition, the DNA-binding domain and two transactivation regions were identified by fusing these isolated domains to previously defined domains of heterologous transcription factors. While most single base alterations in the GATA core sequence eliminated activity, an A to C change in position four, creating a GATC core, was found to increase activity significantly. The deleted ELT-1 protein containing only the C-terminal Zn finger was sufficient for activation in response to GATA, but both fingers were required for activation at GATC. A variety of sites with non-optimal sequences surrounding the GATA core also were found to be excluded better by the protein containing both Zn fingers. Furthermore, a fusion protein containing the entire ELT-1 DNA binding domain fused to the VP16 activation domain was found to have an even greater preference for the GATC core, as well as the optimal flanking bases. We conclude that, although ELT-1 having only its C-terminal finger is capable of activation in response to the WGATAR site, the presence of the upstream finger supplies additional base specificity.
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PMID:Activity of a C. elegans GATA transcription factor, ELT-1, expressed in yeast. 747 42

Fli-1, an ets related gene, was found to be rearranged in 75% of erythroleukemias induced by Friend murine leukemia virus. We have shown previously that the Fli-1 gene codes for a sequence specific transcriptional activator which contains two autonomous transcriptional activation domains, one at the amino terminal region and the other at the carboxy terminal region. Recently human Fli-1 gene was shown to be involved in Ewing's sarcoma and related subtypes of primitive neuroectodermal tumors which share t(11;22) (q24;q12) chromosome translocation. In these tumors the carboxyl terminal region of Fli-1 was found to be fused with the amino terminal region of a putative RNA binding protein, EWS. Because part of the amino terminal transcriptional activation domain of Fli-1 was replaced with the amino terminal domain of the EWS (NTD-EWS) which shares homology with RNA polymerase II, it was speculated that NTD-EWS may interfere with RNA pol II function. Alternatively, NTD-EWS could also contribute to the transcriptional activation function of EWS/Fli-1 chimeric protein by providing either a modulatory/regulatory domain or a novel transcriptional activation domain. Here we show that EWS/Fli-1 chimeric protein functions as a transcriptional activator. Deletion analysis reveals that the EWS domain functions as a modulatory/regulatory domain for the transcriptional activation properties of the carboxy terminal transcriptional activation domain of EWS/Fli-1. We therefore propose that replacement of the amino terminal transcriptional activation domain of the Fli-1 protein with the regulatory domain of NTD-EWS results in the activation of the carboxy terminal transcriptional activation domain of Fli-1 which may be the molecular mechanism involved in these human tumors.
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PMID:EWS/Fli-1 chimeric protein is a transcriptional activator. 750 13

Alveolar rhabdomyosarcoma (ARMS) is characterized cytogenetically by a t(2;13)(q35;q14) chromosomal translocation involving two transcription factor genes: PAX3 and FKHR. ARMS cells express a PAX3-FKHR fusion protein containing the complete N-terminal, DNA-binding domain of PAX3 and the C-terminus of FKHR. Recently we demonstrated that PAX3-FKHR is a more potent transcriptional activator than PAX3 despite impaired binding to canonical PAX3 binding sites. Therefore, we propose that the gene fusion results in switching of PAX3 and FKHR transactivation domains with distinct structure, potency or function. To compare the PAX3 and putative PAX3-FKHR transactivation domains, we fused C-terminal test fragments to the heterologous GAL4 DNA-binding domain and tested activation of a reporter gene co-transfected into four cell types. GAL4-PAX3 and GAL4-PAX3-FKHR were found to be potent activators exhibiting different concentration-dependent transactivation profiles and distinct structural motifs. Deletion mapping demonstrated essential acidic and/or serine/threonine-rich domains in the extreme 3' ends of their respective coding regions and positive modifying elements in adjacent 5' sequences. These data demonstrate that PAX3 and PAX3-FKHR contain structurally distinct transcriptional activation domains and suggest that a consequent difference in function is important for oncogenesis.
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PMID:Wild type PAX3 protein and the PAX3-FKHR fusion protein of alveolar rhabdomyosarcoma contain potent, structurally distinct transcriptional activation domains. 762 19

In Fusarium sporotrichioides, several genes required for biosynthesis of the trichothecene mycotoxin T-2 toxin are closely linked. Further characterization of this gene cluster has revealed a gene, Tri6, that specifies a 217-amino-acid protein with regions similar to Cys2His2 zinc finger proteins. Temporal expression of Tri6 is similar to that of trichothecene biosynthetic pathway genes. Analysis of Tri6 transcripts indicated that transcription is initiated in two regions and that within each region there may be at least four initiation sites. Disruption of Tri6 resulted in a mutant that did not produce trichothecenes but that did accumulate low levels of the trichothecene precursor trichodiene. The Tri6 mutant was unable to convert six trichothecene biosynthetic intermediates to T-2 toxin, and transcription of two biosynthetic genes, Tri4 and Tri5, was greatly reduced in the mutant relative to the wild type. In addition, the product of Tri6 functioned as a transcriptional activator in Saccharomyces cerevisiae when fused to the DNA binding region of GAL4. These results indicate that Tri6 encodes a protein involved in the transcriptional regulation of trichothecene biosynthetic genes in F. sporotrichioides.
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PMID:Tri6 encodes an unusual zinc finger protein involved in regulation of trichothecene biosynthesis in Fusarium sporotrichioides. 764 28

Interferon consensus sequence binding protein (ICSBP) is a member of the interferon regulatory factor (IRF) family of proteins that include IRF-1, IRF-2, and ISGF3gamma which share sequence similarity at the putative DNA binding domain (DBD). ICSBP is expressed exclusively in cells of the immune system and acts as a repressor of interferon consensus sequence (ICS) containing promoters that can be alleviated by interferons. In this communication, we have searched for functional domains of ICSBP by dissecting the DBD from the repression activity. The putative DBD of ICSBP (amino acids 1-121) when fused in frame to the transcriptional activation domain of the herpes simplex VP16 (ICSBP-VP16) is a very strong activator of ICS-containing promoters. In addition, ICSBP-VP16 fusion construct transfected into adenovirus (Ad) 12 transformed cells enabled cell surface expression of major histocompatibility complex class I antigens as did treatment with interferon. On the other hand, the DBD of the yeast transcriptional activator GAL4 was fused in frame to a truncated ICSBP in which the DBD was impaired resulting in a chimeric construct GAL4-ICSBP. This construct is capable of repressing promoters containing GAL4 binding sites. Thus, ICSBP contains at least two independent domains: a DBD and a transcriptional repressor domain. Furthermore, we have tested possible interactions between ICSBP and IRFs. The chimeric construct GAL4-ICSBP inhibited the stimulated effect of IRF-1 on a reporter gene, implying for a possible interaction between IRF-1 and ICSBP. Electromobility shift assays, demonstrated that ICSBP can associate with IRF-2 or IRF-1 in vitro as well as in vivo. Thus, ICSBP contains a third functional domain that enables the association with IRFs. These associations are probably important for the fine balance between positive and negative regulators involved in the interferon-mediated signal transduction pathways in cells of the immune system.
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PMID:Functional domain analysis of interferon consensus sequence binding protein (ICSBP) and its association with interferon regulatory factors. 776

Transcription of the genes necessary for sulfur amino acid biosynthesis in Saccharomyces cerevisiae is dependent on Met4, a transcriptional activator that belongs to the basic region-leucine zipper protein family. In this report, we show that one mechanism permitting the repression of the sulfur network by S-adenosylmethionine (AdoMet) involves inhibition of the transcriptional activation function of Met4. Using a wide array of deleted LexA-Met4 fusion proteins as well as various Gal4-Met4 hybrids, we identify the functional domains of Met4 and characterize their relationship. Met4 appears to contain only one activation domain, located in its N-terminal part. We demonstrate that this activation domain functions in a constitutive manner and that AdoMet responsiveness requires a distinct region of Met4. Furthermore, we show that when fused to a heterologous activation domain, this inhibitory region confers inhibition by AdoMet. Met4 contains another distinct functional domain that appears to function as an antagonist of the inhibitory region when intracellular AdoMet is low. On the basis of the presented results, a model for intramolecular regulation of Met4 is proposed.
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PMID:Functional analysis of Met4, a yeast transcriptional activator responsive to S-adenosylmethionine. 779 28

Promoter analysis was performed on the Rhizopus niveus 3-phosphoglycerate kinase 2-encoding gene (pgk2), one of the two pgk genes (pgk1 and pgk2) from this filamentous fungus sequenced so far. Deletion mutants of the promoter region were fused to the Escherichia coli uidA gene (which codes for beta-glucuronidase; GUS), and introduced into R. niveus to measure the intracellular GUS activities of the transformants. Deletion of the sequence between nt -174 to -133 (numbers indicate the position from the putative translation start codon) caused a significant decrease in the ratio of the GUS activity of the transformant cultured in glucose medium compared to that in glycerol medium. In this region, a 21-nt sequence which is well conserved between pgk1 and pgk2 is present. When it was inserted into the promoter region of the uninducible gene encoding RNase Rh of R. niveus, ligated in front of uidA and introduced into R. niveus, the GUS activity of the transformant was greatly induced by glucose, but less by glycerol. We therefore suggest that the 21-nt sequence is a glucose-inducible transcriptional activator of R. niveus. This is the first report on a transcriptional activator in zygomycetes.
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PMID:Analysis of the 3-phosphoglycerate kinase 2 promoter in Rhizopus niveus. 782 18


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