Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An in vivo selection system for isolating targets of DNA binding proteins in yeast was developed and used to identify the DNA binding site for the NGFI-B protein, a member of the steroid-thyroid hormone receptor superfamily. The feasibility of the technique was verified by selecting DNA fragments that contained binding sites for GCN4, a well-characterized yeast transcriptional activator. The DNA binding domain of NGFI-B, expressed as part of a LexA-NGFI-B-GAL4 chimeric activator, was then used to isolate a rat genomic DNA fragment that contained an NGFI-B binding site. The NGFI-B response element (NBRE) is similar to but functionally distinct from elements recognized by the estrogen and thyroid hormone receptors and the hormone receptor-like proteins COUP-TF, CF1, and H-2RIIBP. Cotransfection experiments in mammalian cells demonstrated that NGFI-B can activate transcription from the NBRE with or without its putative ligand binding domain.
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PMID:Identification of the DNA binding site for NGFI-B by genetic selection in yeast. 192 41

The Tax protein of human T-cell leukemia virus is a potent transcriptional activator of viral and cellular genes, including the genes for interleukin 2 and interleukin 2 receptor alpha chain (IL2R alpha). The NF-kappa B protein has been implicated in Tax-mediated activation of IL2R alpha gene expression. We show that activation of NF-kappa B by Tax is an indirect process that requires prior activation of a preexistent factor that is present in lymphoid cells. Deletion mutagenesis revealed that the carboxyl-terminal acidic region of Tax is required for activation of IL2R alpha-directed gene expression but dispensable for activation of the long terminal repeat (LTR). Our findings suggest that activation of viral and cellular gene expression by Tax is achieved through a cascade of events that involves multiple protein-protein associations and that the specificity of these associations is conferred through different domains of the Tax protein.
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PMID:Activation of NF-kappa B by the HTLV-I trans-activator protein Tax requires an additional factor present in lymphoid cells. 248 94

The b gene of maize encodes a transcriptional activator of anthocyanin pigment biosynthetic genes. Certain b alleles undergo paramutation: a unidirectional, heritable alteration of one allele caused by the presence of another allele. B-I (intensely pigmented plant) is always changed to B' (weakly pigmented plant) in the B'/B-I heterozygote, such that all progeny receive the B' allele. The "new" B', which was B-I in the previous generation, is weakly pigmented and fully capable of changing another B-I allele into B'. It was not previously known whether paramutation is associated with altered b expression, altered B protein function or both. Our results show that B' acts in trans to suppress the transcription of B-I, with transcription remaining low in subsequent generations, even when the original B' allele segregates away. The products of B-I and B' are equally capable of activating the transcription of their target genes, indicating they are functionally equivalent. Genomic restriction maps, DNA sequence and methylation of B' and B-I were compared. Despite dramatic differences in phenotype and transcription of B' and B-I, no evidence for rearrangements, changes in sequence or changes in methylation was found. These results provide no support for models involving "dominant negative" proteins, gene conversion or transposable element interactions. We suggest that b paramutation involves a physical interaction between the alleles that suppresses transcription and promotes a change in chromatin structure that is heritable.
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PMID:Paramutation, an allelic interaction, is associated with a stable and heritable reduction of transcription of the maize b regulatory gene. 750 55

The v-rel oncogene was derived from the c-rel proto-oncogene, which encodes a transcriptional activator. Expression of v-rel transforms avian hematopoietic cells and fibroblasts. Here we report that overexpression (via a replication-competent retroviral vector) of full-length c-Rel as well as a 40-amino-acid, carboxy-terminal deletion construct of c-Rel (c-Rel delta) resulted in the morphological transformation of chicken embryo fibroblasts (CEFs). Subcellular localization of Rel polypeptides in these transformed cells as determined by immunofluorescence and immunoprecipitation revealed their presence in both the nucleus and the cytoplasm, with the majority of Rel polypeptides showing cytoplasmic localization. Cytoplasmic localization could be due to interaction with I kappa B molecules, and in fact, the overexpression of c-Rel or the C-terminal deletion construct of c-Rel resulted in an increase in the levels of mRNA encoding the avian I kappa B protein pp40 and the avian homolog of the NF-kappa B protein, p105. However, expression of v-Rel resulted in the induction of pp40 mRNA only. While c-Rel was a weak activator of kappa B-mediated transcription of a reporter construct in transformed CEFs, v-Rel and c-Rel delta were transcriptional repressors. However, in spite of these differences, all of these proteins resulted in the transformation of CEFs.
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PMID:Transformation of avian fibroblasts overexpressing the c-rel proto-oncogene and a variant of c-rel lacking 40 C-terminal amino acids. 813 92

HeLa cells contain a DNA-binding activity which associates with a kappa B-like DNA element, termed Rel-related protein-binding element (RRBE), localized upstream of the human urokinase promoter. We have purified this activity from the HeLa cell cytosol and have shown that it represents a performed heteromeric complex between p65 (RelA) and c-Rel. Coexpression of c-Rel and p65 (RelA) by in vitro translation formed a DNA-binding complex indistinguishable from purified cellular c-Rel-p65 (RelA) in mobility shift assays. The c-Rel-p65 (RelA) complex was also formed in COS7 cells upon coexpression of c-Rel and p65 (RelA) cDNAs. Cotransfection experiments with COS7 cells, using expression plasmids encoding p50, p65 (RelA), or c-Rel and reporter constructs containing a trimerized RRBE, revealed that c-Rel-p65 (RelA) is a potent activator of the RRBE, giving rise to transcriptional activity higher than that observed with NF-kappa B (p50-p65). In the cytosol, the c-Rel-p65 (RelA) complex existed in a latent, non-DNA-binding form but could be activated by detergent treatment, suggesting that it was associated with an I kappa B protein. Recombinant I kappa B-alpha inhibited the DNA-binding activity of c-Rel-p65 (RelA) via association with either c-Rel or p65 (RelA). Finally, NF-kappa B and c-Rel-p65 (RelA) complexes were found to be differentially expressed and regulated in different cells. The two complexes were present in equimolar amounts in HeLa cells and K562 cells. Stimulation with tetradecanoyl phorbol acetate (TPA) resulted in the nuclear translocation of both NF-kappa B and c-Rel-p65 (RelA) in HeLa cells and of NF-kappa B in HepG2 cells but had no effect on either complex in K562 cells. In addition, TPA stimulation of HepG2 cells induced the expression of a cytosolic latent c-Rel-p65 (RelA) complex which, however, was not translocated to the nucleus. In conclusion, our findings show that c-Rel-p65 (RelA) is an inducible and very potent transcriptional activator which is differentially activated in a cell-type-specific manner.
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PMID:Purification, reconstitution, and I kappa B association of the c-Rel-p65 (RelA) complex, a strong activator of transcription. 813 61

We have examined the effects of an adenosine 3',5'-cyclic monophosphate (cAMP) analog on human aldolase C gene expression in the rat pheochromocytoma cell line PC12. Incubation for 4 h with 500 microM 8-Br-cAMP increased aldolase C mRNA expression 2.5-fold and the expression was still above basal level 24 h later. Using transient transfection experiments we demonstrate that the distal element D in the promoter region of the human aldolase C gene, which binds a transcriptional activator (NGFI-B), is involved in this regulation. NGFI-B mRNA and protein expression were promptly (15 min) increased after 8-Br-cAMP treatment and precedes aldolase C mRNA increase (30 min). After 4 h of 8-Br-cAMP treatment, the binding of NGFI-B protein to the distal element D in the distal promoter region was increased twofold and this correlates with the increased expression of the clone that contains distal element D. These results indicate that the distal element D in the promoter region of the human aldolase C gene is the target of a cAMP-dependent regulation pathway.
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PMID:Human aldolase C gene expression is regulated by adenosine 3',5'-cyclic monophosphate (cAMP) in PC12 cells. 1209 85