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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of promoters by multiple transcription factors might occur through favorable contacts of the activators with themselves or RNA polymerase, or by changes in DNA geometry that enhance formation of the transcription complex. Transcription of the Escherichia coli uhpT gene, encoding the organophosphate transporter, requires the response regulator UhpA and is stimulated by the global regulator protein CAP. CAP binds to the uhpT promoter at a single site, centered at -103.5 bp relative to the start of transcription, and UhpA binds to multiple sites between positions -80 and -32. Overexpression of UhpA did not reduce the degree of CAP stimulation of uhpT-lacZ expression, showing that CAP action is more complex than enhancement of the binding of UhpA. Footprinting experiments demonstrated that UhpA and CAP modestly stimulated each other's binding to the uhpT promoter, but did not affect the positioning of the binding sites. An in vitro transcription system was used to examine the contribution of each transcription factor at the uhpT promoter. Action of UhpA and CAP proteins was not affected by template supercoiling. Kinetic analyses of productive and abortive initiation showed that CAP acted both to stabilize by fivefold the open promoter complexes formed in the presence of UhpA and to enhance by twofold the rate of their formation. These results indicate that open complex formation requires UhpA and that CAP stabilizes the open complex.
J Mol Biol 1999 Oct 08
PMID:Separate contributions of UhpA and CAP to activation of transcription of the uhpT promoter of Escherichia coli. 1051 97

Expression of the D(1A) dopamine receptor in brain is restricted to specific neuronal populations. To investigate the mechanism of this selective expression, we localized a silencer upstream of the human D(1A) gene and identified its binding transcription factor in the D(1A)-negative neural cell line Neuro2a. Using deletion CAT analysis, we narrowed this silencer to the region between nucleotides -561 and -532 relative to the CAP site. This 30-bp region, designated D1AS1, contains a sequence homologous to the AP-2 binding site and binds to a factor that also interacts with the AP-2 consensus sequence. In gel supershift assays, this factor is recognized by anti-AP-2beta antibody. Co-transfection of Neuro2a cells with an AP-2beta expression vector repressed the basal CAT activity of D(1A) promoter-reporter plasmids in a D1AS1-dependent manner. RT-PCR analysis indicated that, among AP-2 family members, Neuro2a cells express only AP-2beta. Furthermore, co-transfection of these cells with decoy oligonucleotides corresponding to the D1AS1 sequence de-repressed the D(1A) gene promoter. Unlike in Neuro2a cells, AP-2beta could not repress the D(1A) promoter in the D(1A)-positive neural cell line, NS20Y. In addition, the expression of AP-2beta in different brain regions does not inversely correlate with that of D(1A) dopamine receptor. These observations taken together indicate that AP-2beta is a repressive transcription factor that acts on the D1AS1 silencer of the D(1A) dopamine receptor gene via some cell-specific mechanism(s) in Neuro2a.
Brain Res Mol Brain Res 1999 Dec 10
PMID:AP-2beta represses D(1A) dopamine receptor gene transcription in neuro2a cells. 1064 Jun 92

The wild-type Escherichia coli bgl promoter is silent in vivo but active in vitro. Silencing in vivo is directed by silencer sequences that flank the promoter, and requires nucleoid-associated protein H-NS and other unidentified cellular factors. Here we show that the DNA bending protein FIS is a repressor of the bgl promoter. Two FIS binding sites, centred at positions -52 and -27, overlap the CAP binding site and the -35 box respectively. FIS efficiently competes with CAP for binding to the wild-type promoter. However, FIS does not prevent binding of RNA polymerase. It interferes with the formation of a heparin-resistant complex and represses transcription initiation up to 40-fold. The presence of CAP has very little effect on the FIS-mediated repression of the wild-type bgl promoter in vitro. However, when a bgl promoter allele was tested that carries an improved CAP binding site (which leads to activation in vivo) CAP effectively counteracted repression by FIS in vitro. These results suggest that FIS contributes to silencing of the wild-type bgl promoter in vivo, presumably in the early exponential phase when FIS is predominantly expressed.
Mol Microbiol 2000 Apr
PMID:Antagonistic control of the Escherichia coli bgl promoter by FIS and CAP in vitro. 1076 Jan 65

Metal complexes of general formula Na2M(CAP)2xH2O (with M = Cd(II) or Ni(II), x = 7 and 4, respectively, CAP = 1-(D-3-mercapto-2-methylpropionyl)-L-proline) and NaCuCAPx3H2O have been synthesized as amorphous compounds and studied by means of X-ray photoelectron spectroscopy (XPS). Cu(I) derivative has been studied by IR, XPS and large-angle X-ray scattering (LAXS). IR data and the chemical shift of core level signals suggest that CAP is bonded to the metal via the sulphur atom and the carbonylic oxygen. LAXS data confirm this finding and are consistent with a tetrahedral configuration around the copper ion. The CAP molecule is bonded through the sulphur and the carbonylic oxygen and two water molecules complete the coordination around the metal. The sodium ion exhibits a tetrahedral configuration and interacts with the carboxylic group and two water molecules. One of these is bridging bonded between copper and sodium. No metal-nitrogen bonds are present.
Spectrochim Acta A Mol Biomol Spectrosc 2000 Feb 15
PMID:X-ray photoelectron spectra of complexes with 1-(D-3-mercapto-2-methylpropionyl)-L-proline and Ni(II), Cd(II) and Cu(I): synthesis and LAXS study of Cu(I) derivative. 1079 67

Although serum prostate specific antigen (PSA), derived from cellular PSA through secretion, is widely used as a marker for prostate cancer (CAP), the exact regulatory mechanism of its secretion is not fully understood. To explore the regulation of serum PSA concentration, we examined whether the glycosylation state of cellular PSA might be associated with its secretion, thus determining its serum concentration. Blood and prostate tissue specimens were obtained from patients undergoing radical prostatectomy. Following preparation of cell extracts by tissue homogenization, the concentrations of serum and cellular PSA were determined using the Tandem-E PSA kit. The extent of cellular PSA glycosylation was then assessed by Western blot and affinoblott analyses. Neither serum nor cellular PSA concentrations correlated with the Gleason scores. Similarly, no direct relation between serum and cellular PSA levels was observed. However, the Western blots showed that the cellular PSA proteins were converted to the deglycosylated forms with glycosidase treatment, indicating differential glycosylation of cellular PSA. Affinoblotting further revealed that the various amounts of PSA glycosylation were associated wtih the serum PSA levels, with an inverse correlation between serum PSA and cellular PSA glycosylation: the greater the PSA glycosylation, the lower the serum PSA, and vice versa. The present study demonstrates that cellular PSAs in CAP specimens are differentially glycosylated and that such difference correlates well with the serum PSA concentration. Therefore, the concentrations of serum PSA appear to depend in part on a selective secretion of cellular PSA, which could be regulated primarily by its glycosylation state.
Mol Urol 1999
PMID:Differential Glycosylation of Cellular Prostate Specific Antigen and the Regulatory Mechanism of Its Secretion. 1085 17

A region of the genome of the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120 containing the ntcB gene was identified. This region is located upstream from the nir operon involved in nitrate assimilation in this cyanobacterium. An Anabaena ntcB mutant was able to use ammonium and dinitrogen as sources of nitrogen for growth but was unable to assimilate nitrate. Enzymes of the nitrate reduction system were not synthesized in the ntcB mutant under derepression conditions. The transcription start-point of the Anabaena nir operon, which has been shown to be subjected to ammonium-stimulated repression and whose expression requires the global nitrogen regulator NtcA, was only weakly used in the ntcB mutant. The expression of the ntcB gene in strain PCC 7120 was also subjected to repression by ammonium and was found to take place from an NtcA-activated promoter located 31 bp upstream from the start of the ntcB gene. NtcB binds to the nir promoter region in vitro and protects a region localized just upstream from the NtcA-binding site in footprinting assays. These results showed that NtcB, a LysR-family protein, is required in addition to NtcA, a CAP-family protein, for the expression of genes encoding proteins specifically involved in nitrate assimilation in Anabaena sp. PCC 7120.
Mol Microbiol 2000 Nov
PMID:Activation of the Anabaena nir operon promoter requires both NtcA (CAP family) and NtcB (LysR family) transcription factors. 1106 84

Cac3p/Msi1p, the Saccharomyces cerevisiae homolog of retinoblastoma-associated protein 48 (RbAp48), is a component of chromatin assembly factor I (CAF-I), a complex that assembles histones H3 and H4 onto replicated DNA. CAC3 overexpression also suppresses the RAS/cyclic AMP (cAMP) signal transduction pathway by an unknown mechanism. We investigated this mechanism and found that CAC3 suppression of RAS/cAMP signal transduction was independent of either CAC1 or CAC2, subunits required for CAF-I function. CAC3 suppression was also independent of other chromatin-modifying activities, indicating that Cac3p has at least two distinct, separable functions, one in chromatin assembly and one in regulating RAS function. Unlike Cac1p, which localizes primarily to the nucleus, Cac3p localizes to both the nucleus and the cytoplasm. In addition, Cac3p associates with Npr1p, a cytoplasmic kinase that stablizes several nutrient transporters by antagonizing a ubiquitin-mediated protein degradation pathway. Deletion of NPR1, like overexpression of Cac3p, suppressed the RAS/cAMP pathway. Furthermore, NPR1 overexpression interfered with the ability of CAC3 to suppress the RAS/cAMP pathway, indicating that extra Cac3p suppresses the RAS/cAMP pathway by sequestering Npr1p. Deletion of NPR1 did not affect the quantity, phosphorylation state, or localization of Ras2p. Consistent with the idea that Npr1p exerts its effect on the RAS/cAMP pathway by antagonizing a ubiquitin-mediated process, excess ubiquitin suppressed both the heat shock sensitivity and the sporulation defects caused by constitutive activation of the RAS/cAMP pathway. Thus, CAC3/MSI1 regulates the RAS/cAMP pathway via a chromatin-independent mechanism that involves the sequestration of Npr1p and may be due to the increased ubiquitination of an Npr1p substrate.
Mol Cell Biol 2001 Mar
PMID:CAC3(MSI1) suppression of RAS2(G19V) is independent of chromatin assembly factor I and mediated by NPR1. 1123 15

NagC and Mlc are paralogous transcriptional repressors in E.coli. Unexpectedly they possess almost identical amino acid sequences in their helix-turn-helix (H-T-H), DNA binding motif and they bind to very similar consensus operator targets. Binding to each others sites can be demonstrated in vitro but no cross regulation can be detected in vivo with physiological amounts of the two proteins. Although both proteins are involved in regulating the expression of PTS genes, the characteristics of their repression and induction are very different. NagC is a dual-function, activator-repressor which co-ordinates the metabolism of the amino sugars, N-acetylglucosamine (GlcNAc) and glucosamine, by repressing the divergent nagE-BA operons and by activating the glmUS operon. Repression (and activation) by NagC requires that NagC binds simultaneously to two operators, thus forming a DNA loop. This chelation effect allows use of lower affinity sites which would not individually bind the repressor. The specific inducer for NagC is GlcNAc-6-P, the product of GlcNAc transport by the PTS and a key compound in amino sugar metabolism. Mlc represses several genes implicated in the uptake of glucose; ptsG, ptsHI and manXYZ, and malT, the activator of the mal regulon. Glucose behaves like the inducer but growth on glucose only produces an overall increase in expression for ptsG and ptsHI. All Mlc repressed genes are also controlled by cAMP/CAP, so that glucose affects their transcription in two opposing ways: increasing expression by acting as the inducer for Mlc but decreasing expression by lowering the cAMP/CAP concentration. The Mlc protein is not directly responsive to glucose per se but to the activity status of the PTS. Displacement of Mlc from its binding sites occurs during growth on glucose and other PTS sugars and involves sequestration of the repressor to membranes by binding to dephosphorylated PtsG.
J Mol Microbiol Biotechnol 2001 Jul
PMID:Regulation of PTS gene expression by the homologous transcriptional regulators, Mlc and NagC, in Escherichia coli (or how two similar repressors can behave differently). 1136 Oct 67

We have surveyed the publicly available genome sequence of Corynebacterium diphtheriae (www.sanger.ac.uk) to identify components of the phosphotransferase system (PTS), which plays a central role in carbon metabolism in many bacteria. Three gene loci were found to contain putative pts genes. These comprise: (i) the genes of the general phosphotransferases enzyme I (ptsI) and HPr (ptsH), a fructose-specific enzyme IIABC permease (fruA), and a fructose 1-phosphate kinase (fruK); (ii) a gene that encodes an enzyme IIAB of the fructose/mannitol family, and a novel HPr-like gene, ptsF, that encodes an HPr domain fused to a domain of unknown function; (iii) and a gene for a glucose-specific enzyme IIBCA (ptsG). A search for genes that may be putative PTS-targets or that may operate in general carbon regulation revealed a possible regulatory gene encoding an antiterminator protein downstream from ptsG. Furthermore, genes were detected encoding glycerol kinase, glucose kinase, and a homologue of the global activator of carbon catabolite repression in Escherichia coli, CAP. The possible significance of these observations in carbon metabolism and the novel features of the detected genes are discussed.
J Mol Microbiol Biotechnol 2001 Jul
PMID:Corynebacterium diphtheriae: a PTS view to the genome. 1136 Oct 72

Multiple transcription start sites were identified in the human gonadotropin releasing hormone receptor (hGnRHR) gene. Recently, an upstream promoter residing at -1727/-1674, in vicinity of a CAP site at -1673, was characterized. In this report, we elucidated the underlying mechanisms for the regulation of this promoter. Functionally, this promoter was constitutively suppressed by a silencer element (-1673/-1351) situated immediately downstream to it. On the other hand, pituitary adenylate cyclase-activating polypeptide (PACAP), via the cAMP pathway, was found to be the extracellular cue to control the upstream promoter. Following PACAP-27, PACAP-38 (30 nM) and forskolin (25 microM) treatment, there were significant increases in the reporter gene activities. By deletion analysis, the region residing at -1727 to -1577, containing the distal promoter and 97 bp of the silencer was subsequently found to be responsible for PACAP/cAMP induction. To localize the PACAP-dependent cis-acting element(s) within the silencer, block replacement scanning mutation was performed and a hGnRHR gene PACAP-responsive element (GPRE) was identified at -1676/-1648. The actions of PACAPs and forskolin on the GPRE were further evidenced by gel mobility shift assays. There was an increase in protein binding onto this element only after peptide treatment. As GnRH receptor number on gonadotrope cell surface is a key factor in regulating gonadotropin release, the present study provides an insight into the interplay between PACAP and GnRH receptors on pituitary gonadotropes to control human reproductive functions.
Mol Cell Endocrinol 2001 May 15
PMID:Interplay of pituitary adenylate cyclase-activating polypeptide with a silencer element to regulate the upstream promoter of the human gonadotropin-releasing hormone receptor gene. 1136 53


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