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)

All organisms respond to a sudden increase in temperature by the so-called heat shock response. This response results in the induction of a subset of genes, designated heat shock genes coding for heat shock proteins, which allow the cell to cope with the stress regimen. Research carried out during the last 10 years with eubacteria has revealed that the heat shock genes of a given species fall into different classes (regulons), where each class is regulated by a different transcriptional regulator, which could be an alternative sigma factor, a transcriptional activator, or a transcriptional repressor. All regulons of a single species constitute the heat shock stimulon. In Bacillus subtilis, more than 200 genes representing over 7% of the transcriptionally active genes are induced at least 3-fold in response to a heat shock. This response becomes apparent within the first minute after exposure to heat stress, is transient, and is coordinated by at least 5 transcriptional regulator proteins, including 2 repressors, an alternate sigma-factor, and a 2-component signal transduction system. A detailed analysis of the regulation of all known heat shock genes has shown that they belong to at least 6 regulons that together comprise the B. subtilis heat shock stimulon. Potential thermosensors are discussed in this article.
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PMID:The Bacillus subtilis heat shock stimulon. 1498 53

Sox proteins are DNA-binding proteins belonging to the HMG box superfamily and they play key roles in animal embryonic development. Zebrafish Sox21a is part of group B Sox proteins and its chicken and mouse orthologs have been described as transcriptional repressor and activator, respectively, in two different target gene contexts. Zebrafish sox21a is present as a maternal transcript in the oocyte and is mainly expressed at the developing midbrain-hindbrain boundary from the onset of neurulation. In order to understand its role in vivo, we ectopically expressed sox21a by microinjection. Ectopic expression of full length sox21a leads to dorsalization of the embryos. A subset of the dorsalized embryos shows a partial axis splitting, and hence an ectopic neural tube, as an additional phenotype. At gastrulation, injected embryos show expansion of the expression domains of organizer-specific genes, such as chordin and goosecoid. Molecular markers used in somitogenesis highlight that sox21a-injected embryos have shortened AP axis, undulating axial structures, enlarged or even radialized paraxial territory. The developmental abnormalities caused by ectopic expression of sox21a are suggestive of defects in convergence-extension morphogenetic movements. Antisense morpholino oligonucleotides, designed to functionally knockdown sox21a, cause ventralization of the embryos. Moreover, gain-of-function experiments with chimeric constructs, where Sox21a DNA-binding domain is fused to a transcriptional activator (VP16) or repressor (EnR) domain, suggests that zebrafish Sox21a acts as a repressor in dorso-ventral patterning.
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PMID:Ectopic expression and knockdown of a zebrafish sox21 reveal its role as a transcriptional repressor in early development. 1503 15

The molecular mechanism by which GA regulates plant growth and development has been a subject of active research. Analyses of the rice (Oryza sativa) genomic sequences identified 77 WRKY genes, among which OsWRKY71 is highly expressed in aleurone cells. Transient expression of OsWRKY71 by particle bombardment specifically represses GA-induced Amy32b alpha-amylase promoter but not abscisic acid-induced HVA22 or HVA1 promoter activity in aleurone cells. Moreover, OsWRKY71 blocks the activation of the Amy32b promoter by the GA-inducible transcriptional activator OsGAMYB. Consistent with its role as a transcriptional repressor, OsWRKY71 is localized to nuclei of aleurone cells and binds specifically to functionally defined TGAC-containing W boxes of the Amy32b promoter in vitro. Mutation of the two W boxes prevents the binding of OsWRKY71 to the mutated promoter, and releases the suppression of the OsGAMYB-activated Amy32b expression by OsWRKY71, suggesting that OsWRKY71 blocks GA signaling by functionally interfering with OsGAMYB. Exogenous GA treatment decreases the steady-state mRNA level of OsWRKY71 and destabilizes the GFP:OsWRKY71 fusion protein. These findings suggest that OsWRKY71 encodes a transcriptional repressor of GA signaling in aleurone cells.
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PMID:A rice WRKY gene encodes a transcriptional repressor of the gibberellin signaling pathway in aleurone cells. 1504 97

We previously identified a regulatory element at the 3'-downstream region of the human angiotensinogen (hANG) gene. Using this element as a probe by the Southwestern screening, we isolated a cDNA clone, encoding Finb, a transcriptional activator with multiple zinc finger domains. The N-terminal zinc finger domain of Finb bound to the GGATGG sequence within the regulatory element. Unexpectedly, Finb repressed transcription dependent on the regulatory element. Inspection of the 5'-flanking region in the hANG promoter identified the GGATGG-like elements, which prompted us to examine the effect of Finb on the hANG promoter activity. We also found the two Finb binding elements in the 5'-flanking region of the hANG gene by the gel shift assay, both of which were necessary for transcriptional repression of the hANG promoter. These findings suggest that Finb functions as a sequence-specific transcriptional repressor of the hANG gene.
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PMID:Finb, a multiple zinc finger protein, represses transcription of the human angiotensinogen gene. 1506 62

Promyelocytic leukaemia nuclear bodies (PML NBs) are structured protein complexes associated with the nuclear matrix. PML constitutes the scaffold component of NBs and recruits onto these domains a striking variety of proteins, many of which are involved in apoptosis control. Several reports have directly implicated PML in apoptosis and senescence, but the mechanisms by which these are conveyed are still largely unsettled. Recruitment of partner proteins onto NBs is regulated by PML sumolation, a specific post-translational modification also found in many NB-associated proteins. Among these, several are implicated in transcription repression or activation, like the transcriptional repressor Daxx or the transcriptional activator P53. Whether NBs constitute platforms where active sites of enzymatic modifications are carried out, as suggested for P53, sites of intranuclear protein sequestration, as proposed for Daxx or organelles specialized in catabolism, is still debated. A variety of stress-related signalling pathways dramatically modulate the formation of PML NBs, which may provide a clue as to their physiological function.
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PMID:PML nuclear bodies and apoptosis. 1507 45

The E4BP4 basic leucine zipper (bZIP) transcription factor is regulated by interleukin-3 (IL-3) in pro-B cells and has been reported to promote survival of the murine IL-3-dependent pro-B cell lines, FL5.12 and Baf-3. The E2A-HLF oncoprotein arises from a t(17;19) translocation in childhood pro-B cell acute lymphoblastic leukaemia and acts as an anti-apoptotic factor in FL5.12 and Baf-3 cells. To assess the functions of E2A-HLF and E4BP4 in cell survival, a tetracycline-inducible system was established in Baf-3 cells to express E4BP4 or E2A-HLF. Upon IL-3 withdrawal, expression of E2A-HLF conferred resistance to apoptosis whereas overexpression of E4BP4 did not. E4BP4 and E2A-HLF both recognized the same DNA sequence in reporter gene assays, but had opposite effects on transcription. E2A-HLF acts as a transcriptional activator and E4BP4 as a transcriptional repressor. Furthermore, E4BP4 is a downstream transcriptional target of E2A-HLF. Our data suggests that the overexpression of E4BP4 is unable to block apoptosis induced by IL-3 withdrawal and that the expression of E2A-HLF does not replace the function of E4BP4 in mediating survival.
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PMID:E4BP4 expression is regulated by the t(17;19)-associated oncoprotein E2A-HLF in pro-B cells. 1514 70

Although co-ordinate interaction between different signal transduction pathways is essential for developmental decisions, interpathway connections are often obscured and difficult to identify due to cross-talk. Here signals from the fission yeast stress-activated MAPK Spc1 are shown to regulate Cgs2, a negative regulator of the cAMP-dependent protein kinase (protein kinase A) pathway. Pathway integration is achieved via Spc1-dependent binding of Atf1-Pcr1 heterodimer to an M26 DNA site in the cgs2+ promoter, which remodels chromatin to regulate expression of cgs2+ and targets downstream of protein kinase A. This direct interpathway connection co-ordinates signals of nitrogen and carbon source depletion to affect a G0 cell-cycle checkpoint and sexual differentiation. The Atf1-Pcr1-M26 complex-dependent chromatin remodeling provides a molecular mechanism whereby Atf1-Pcr1 heterodimer can function differentially as either a transcriptional activator, or as a transcriptional repressor, or as an inducer of meiotic recombination. We also show that the Atf1-Pcr1-M26 complex functions as both an inducer and repressor of chromatin remodeling, which provides a way for various chromatin remodeling-dependent effector functions to be regulated.
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PMID:Atf1-Pcr1-M26 complex links stress-activated MAPK and cAMP-dependent protein kinase pathways via chromatin remodeling of cgs2+. 1544 37

The spatial arrangement of chromatin within the nucleus can affect reactions that occur on the DNA and is likely to be regulated. Here we show that activation of INO1 occurs at the nuclear membrane and requires the integral membrane protein Scs2. Scs2 antagonizes the action of the transcriptional repressor Opi1 under conditions that induce the unfolded protein response (UPR) and, in turn, activate INO1. Whereas repressed INO1 localizes throughout the nucleoplasm, the gene is recruited to the nuclear periphery upon transcriptional activation. Recruitment requires the transcriptional activator Hac1, which is produced upon induction of the UPR, and is constitutive in a strain lacking Opi1. Artificial recruitment of INO1 to the nuclear membrane permits activation in the absence of Scs2, indicating that the intranuclear localization of a gene can profoundly influence its mechanism of activation. Gene recruitment to the nuclear periphery, therefore, is a dynamic process and appears to play an important regulatory role.
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PMID:Gene recruitment of the activated INO1 locus to the nuclear membrane. 1545 74

Mitochondrial glycerol-3-phosphate dehydrogenase (mGPDH) is an essential component of the glycerol phosphate shuttle that transfers reduction equivalents from the cytosol into the mitochondrion. Within the testis, immunohistological analysis localized human mGPDH to late spermatids and to the midpiece of spermatozoa. The expression of human mGPDH is regulated by two somatic promoters, and here, we describe a third testis-specific promoter of human mGPDH. The usage of this testis-specific promoter correlates with the expression of a shortened mGPDH transcript of approximately 2.4 kb in length, which is solely detectable from testicular RNA. Within the testis-specific promoter, we detected a cAMP-response element (CRE) site at -51, which binds the testis-specific transcriptional activator CRE modulator tau (CREMtau) in electrophoretic mobility shift assays. This recognition site overlaps with a nuclear receptor binding half-site at -49, which binds the testis-specific transcriptional repressor germ cell nuclear factor (GCNF). Both factors compete for binding to the same DNA response element. Ectopic expression of CREMtau in HepG2 cells activated a promoter-driven luciferase construct in transient transfection experiments. Additional cotransfection of GCNF relieved this activity, suggesting a down-regulation of CREMtau-mediated activation by GCNF. This effect was preserved by introducing the CRE/nuclear receptor-binding element into a heterologous promoter context. Our data suggest a down-regulation of CREMtau-mediated gene expression by GCNF, which might be a general regulation mechanism for several postmeiotically expressed genes with a temporal expression peak during early spermatid development.
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PMID:Germ cell nuclear factor relieves cAMP-response element modulator tau-mediated activation of the testis-specific promoter of human mitochondrial glycerol-3-phosphate dehydrogenase. 1545 63

Ets transcription factors play crucial roles in regulating diverse cellular processes including cell proliferation, differentiation and survival. Coordinated regulation of the Drosophila Ets transcription factors YAN and POINTED is required for eliciting appropriate responses to Receptor Tyrosine Kinase (RTK) signaling. YAN, a transcriptional repressor, and POINTED, a transcriptional activator, compete for regulatory regions of common target genes, with the ultimate outcome likely influenced by context-specific interactions with binding partners such as MAE. Previous work in cultured cells has led us to propose that MAE attenuates the transcriptional activity of both YAN and POINTED, although its effects on POINTED remain controversial. Here we describe a new layer of complexity to this regulatory hierarchy whereby mae expression is itself directly regulated by the opposing action of YAN and POINTED. In addition, we report that MAE can antagonize POINTED function during eye development; a finding that suggests MAE operates as a dual positive and negative regulator of RTK-mediated signaling in vivo. Together our results lead us to propose that a combination of protein-protein and transcriptional interactions between MAE, YAN and POINTED establishes a complex regulatory circuit that ensures that both down-regulation and activation of the RTK pathway occur appropriately according to specific developmental context.
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PMID:MAE, a dual regulator of the EGFR signaling pathway, is a target of the Ets transcription factors PNT and YAN. 1551 39


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