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)

The proto-oncoprotein SYT is involved in the unique translocation t(X;18) found in synovial sarcoma SYT-SSX fusions. SYT has a conserved N-terminal domain (SNH domain) that interacts with the human paralog of Drosophila Brahma (hBRM) and Brahma-related gene 1 (BRG1) chromatin remodeling proteins and a C-terminal transactivating sequence rich in glutamine, proline, glycine, and tyrosine (QPGY domain). Here we reported the isolation of the ribonucleoprotein SYT-interacting protein/co-activator activator (SIP/CoAA), which specifically binds the QPGY domain of SYT and also the SYT-SSX2 translocation fusion. SIP/CoAA is a general nuclear co-activator and an RNA splicing modulator that contains two RNA recognition motifs and multiple hexapeptide repeats. We showed that the region consisting of the hexapeptide motif (YQ domain) is similar to the hexapeptide repeat domain found in EWS and in TLS/FUS family proteins. The YQ domain also resembles the QPGY region of SYT itself and like all these other domains acts as a transcriptional activator in reporter assays. Most interestingly, the last 84 amino acids adjacent to YQ down-modulate by 25-fold the YQ transactivation of the reporter gene, and both domains are important for SIP/CoAA binding to SYT. In addition, SYT acts together with SIP/CoAA in stimulating estrogen and glucocorticoid receptor-dependent transcriptional activation. Activation is hormone-dependent and requires functional hBRM and/or BRG1. The stimulation is strongly reduced if the N-terminal region of hBRM/BRG1 (amino acids 1-211) is deleted. This region encompasses the SNF11 binding domain (amino acids 156-211), which interacts specifically with SYT in vivo and in vitro.
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PMID:The proto-oncoprotein SYT interacts with SYT-interacting protein/co-activator activator (SIP/CoAA), a human nuclear receptor co-activator with similarity to EWS and TLS/FUS family of proteins. 1622 27

Osterix was identified as a transcription factor expressing, in osteoblasts, required for bone formation. However, the molecular mechanisms of the gene regulation by Osterix remain elusive. In this study, we examined the transactivation property of Osterix by using the Gal4 fusion system reporter assay. We identified the transactivation domain of Osterix, which contains high proline and glycine residues and has an activation property in mammalian and yeast cells. The GST-pull down analysis revealed that the basal transcription factor, TF-IIB, but not TBP, binds to the transactivation domain. Furthermore, we found that Osterix interacts with chromatin remodeling factor, Brg-1, through its C-terminal zinc finger domain in vivo and in vitro. These findings suggest that Osterix possesses functional domains which associate with transcription mediated factors and functions as a transcriptional activator in the nucleus.
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PMID:Molecular characterization of the zinc finger transcription factor, Osterix. 1646 88

Adaptation to low oxygen tension (hypoxia) in cells and tissues leads to the transcriptional induction of a series of genes that participate in angiogenesis, iron metabolism, glucose metabolism, and cell proliferation/survival. The primary factor mediating this response is the hypoxia-inducible factor-1 (HIF-1), an oxygen-sensitive transcriptional activator. HIF-1 consists of a constitutively expressed subunit HIF-1beta and an oxygen-regulated subunit HIF-1alpha (or its paralogs HIF-2alpha and HIF-3alpha). The stability and activity of the alpha subunit of HIF are regulated by its post-translational modifications such as hydroxylation, ubiquitination, acetylation, and phosphorylation. In normoxia, hydroxylation of two proline residues and acetylation of a lysine residue at the oxygen-dependent degradation domain (ODDD) of HIF-1alpha trigger its association with pVHL E3 ligase complex, leading to HIF-1alpha degradation via ubiquitin-proteasome pathway. In hypoxia, the HIF-1alpha subunit becomes stable and interacts with coactivators such as cAMP response element-binding protein binding protein/p300 and regulates the expression of target genes. Overexpression of HIF-1 has been found in various cancers, and targeting HIF-1 could represent a novel approach to cancer therapy.
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PMID:Hypoxia-inducible factor-1 (HIF-1). 1688 34

Whereas about 70 small non-coding RNAs have been found in the Escherichia coli genome, relatively little is known about regulatory RNAs from Gram-positive bacteria. Here, we demonstrate that the recently identified small untranslated RNA SR1 from the Bacillus subtilis genome is a regulatory RNA involved in fine-tuning of arginine catabolism. 2D protein gel electrophoresis indicated three possible SR1 targets that are regulated by the transcriptional activator AhrC, which was shown to be the primary target of SR1. In vitro pairing studies and an in vivo reporter gene test demonstrated a specific interaction between SR1 and ahrC mRNA. This interaction did not lead to degradation of ahrC mRNA, but inhibited translation at a post-initiation stage. Our data show that the Hfq chaperone was not required for the stabilization of SR1 in vivo. The amount of SR1 was increased upon addition of l-arginine and l-ornithine, but not l-citrulline or l-proline.
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PMID:The small untranslated RNA SR1 from the Bacillus subtilis genome is involved in the regulation of arginine catabolism. 1702 May 85

A novel DREB (dehydration responsive element binding protein) homologous gene, GmDREB2, was isolated from soybean. Based on its similarity with AP2 domains, GmDREB2 was classified into A-5 subgroup in DREB subfamily in AP2/EREBP family. Expression of GmDREB2 gene was induced by drought, high salt, and low temperature stresses and abscisic acid treatment. The GmDREB2 bound specifically to DRE element in vitro. Furthermore, the overexpression of GmDREB2 activated expression of downstream genes in transgenic Arabidopsis, resulting in enhanced tolerance to drought and high-salt stresses and did not cause growth retardation. Analysis of free proline contents in transgenic tobacco indicated that the overexpression of GmDREB2 accumulated higher level of free proline compared to the wild type plants under drought condition. The results from this study indicate that this novel soybean GmDREB2 gene functions as an important transcriptional activator and may be useful in improving of plant tolerance to abiotic stresses in plants.
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PMID:GmDREB2, a soybean DRE-binding transcription factor, conferred drought and high-salt tolerance in transgenic plants. 1717 6

The P2 promoter of proP, encoding a transporter for proline and glycine betaine in Escherichia coli, is a unique paradigm, where master regulators of different growth stages, Fis and sigma(S) (RpoS), collaborate to achieve promoter activation. It is also the only case described where Fis functions as class II transcriptional activator (centred at -41). Here we show that the degenerate -35 sequence, and the location of the Fis binding site, which forces a suboptimal 16 bp spacing between the -35 and -10 elements, allow only sigma(S) but not sigma(70) to function at proP (P2). Moreover, the interface between Fis and sigma(S) seems better suited to sigma(S), due to a single residue difference between sigma(S) and sigma(70). Nevertheless, Fis can activate RNA polymerase containing sigma(70) at a proP (P2) promoter variant, in which a typical sigma(70)-35 recognition sequence has been introduced at a 17 bp distance from the -10 hexamer. In summary, we elucidate the rules that govern sigma factor selectivity in the presence of a class II activator, provide new insight into transcriptional activation by Fis from this position, and clarify, why the proP (P2) promoter is precisely activated during a short time window of the growth cycle, when Fis and sigma(S) are both present.
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PMID:The -35 sequence location and the Fis-sigma factor interface determine sigmas selectivity of the proP (P2) promoter in Escherichia coli. 1730 3

It has been reported that mouse Lbh (limb-bud and heart) can regulate cardiac gene expression by modulating the combinatorial activities of key cardiac transcription factors, as well as their individual functions in cardiogenesis. Here we report the cloning and characterization of the human homolog of mouse Lbh gene, hLBH, from a human embryonic heart cDNA library. The cDNA of hLBH is 2927 bp long, encoding a protein product of 105 amino acids. The protein is highly conserved in evolution across different species from zebra fish, to mouse, to human. Northern blot analysis indicates that a 2.9 kb transcript specific for hLBH is most abundantly expressed in both embryonic and adult heart tissue. In COS-7 cells, hLBH proteins are localized to both the nucleus and the cytoplasm. hLBH is a transcription activator when fused to Gal-4 DNA-binding domain. Deletion analysis indicates that both the N-terminal containing proline-dependent serine/threonine kinase group and the C-terminal containing ERK D-domain motif are required for transcriptional activation. Overexpression of hLBH in COS-7 cells activates the transcriptional activities of activator protein-1 (AP-1) and serum response element (SRE). These results suggest that hLBH proteins may act as a transcriptional activator in mitogen-activated protein kinase signaling pathway to mediate cellular functions.
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PMID:A human homolog of mouse Lbh gene, hLBH, expresses in heart and activates SRE and AP-1 mediated MAPK signaling pathway. 1739 Feb 36

The Aspergillus nidulans NIMA kinase is essential for mitosis and is the founding member of the conserved NIMA-related kinase (Nek) family of protein kinases. To gain insight into NIMA function, a copy number suppression screen has been completed that defines three proteins termed MCNA, MCNB, and MCNC (multi-copy-number suppressor of nimA1 A, B, and C). All display a distinctive and dynamic cell cycle-specific distribution. MCNC has weak similarity to Saccharomyces cerevisiae Def1 within a shared CUE-like domain. MCNC, like Def1, is a cytoplasmic protein with slow mobility during sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its deletion causes polarization defects and a small colony phenotype. MCNC enters nuclei during mitosis. In contrast, MCNB is a nuclear protein displaying increased nuclear levels as cells progress through interphase but is lost from nuclei at mitosis. MCNB is highly related to the Schizosaccharomyces pombe forkhead transcription factor Sep1 and is likely a transcriptional activator of nimA. Most surprisingly, MCNA, a protein restricted to the aspergilli and pathogenic systemic dimorphic fungi (the Eurotiomycetes), defines a nuclear body located near nucleoli at the nuclear periphery of G(2) nuclei. During progression through mitosis, the MCNA body is excluded from nuclei. Cytoplasmic MCNA bodies then diminish during early stages of interphase, and single MCNA bodies are formed within nuclei as interphase progresses. Three sites of MCNA phosphorylation were mapped and mutated to implicate proline-directed phosphorylation in the equal segregation of MCNA during the cell cycle. The data indicate all three MCN proteins likely have cell cycle functions.
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PMID:Copy number suppressors of the Aspergillus nidulans nimA1 mitotic kinase display distinctive and highly dynamic cell cycle-regulated locations. 1893 Oct 41

Saccharomyces cerevisiae can utilize high quality (e.g. glutamine and ammonia) as well as low quality (e.g. gamma-amino butyric acid and proline) nitrogen sources. The transcriptional activator Put3p allows yeast cells to utilize proline as a nitrogen source through expression of the PUT1 and PUT2 genes. Put3p activates high level transcription of these genes by binding proline directly. However, Put3p also responds to other lower quality nitrogen sources. As nitrogen quality decreases, Put3p exhibits an increase in phosphorylation concurrent with an increase in PUT gene expression. The proline-independent activation of the PUT genes requires both Put3p and the positively acting GATA factors, Gln3p and Gat1p. Conversely, the phosphorylation of Put3p is not dependent on GATA factor activity. Here, we find that the mutation of Put3p at amino acid Tyr-788 modulates the proline-independent activation of PUT1 through Gat1p. The phosphorylation of Put3p appears to influence the association of Gat1p, but not Gln3p, to the PUT1 promoter. Combined, our findings suggest that this may represent a mechanism through which yeast cells rapidly adapt to use proline as a nitrogen source under nitrogen limiting conditions.
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PMID:Mutation of a phosphorylatable residue in Put3p affects the magnitude of rapamycin-induced PUT1 activation in a Gat1p-dependent manner. 1957 22

Expression of nitrogen metabolism genes is regulated by the quality of the nitrogen supply. Here, we describe a mechanism for the transcriptional regulation of the general amino acid permease gene per1 in Schizosaccharomyces pombe. We show that when ammonia is used as the nitrogen source, low levels of per1 are transcribed and histones in the coding and surrounding regions of per1 are acetylated. In the presence of proline, per1 transcription is upregulated and initiates from a more upstream site, generating 5'-extended mRNAs. Concomitantly, histones at per1 are deacetylated in a Clr6-dependent manner, suggesting a positive role for Clr6 in transcriptional regulation of per1. Upstream initiation and histone deactylation of per1 are constitutive in cells lacking the serine/threonine kinase oca2, indicating that Oca2 is a repressor of per1. Oca2 interacts with a protein homologous to the Saccharomyces cerevisiae transcriptional activator Cha4 and with Ago1. Loss of Cha4 or Ago1 causes aberrant induction of per1 under noninducing conditions, suggesting that these proteins are also involved in per1 regulation and hence in nitrogen utilization.
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PMID:Transcriptional activation of the general amino acid permease gene per1 by the histone deacetylase Clr6 Is regulated by Oca2 kinase. 2040 84


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