Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The physiological and genetic controls operating on phosphate-regulated promoters were studied in greater detail. This was done by defining the control for three phosphate-regulated genes: phoA, psiE, and psiO. Each is highly inducible by phosphate starvation. Individually, these phosphate-starvation-inducible, psi, genes at the same time show common and differing features in their molecular control. The phoA gene, encoding alkaline phosphatase, is specifically induced by phosphate starvation. It is negatively controlled by phoR as well as by the phosphate-specific transport (PST) system in Escherichia coli. phoA induction is positively controlled by the phoB, M, and R products; it is unaffected by the cAMP and CAP system. The psiE and psiO genes were studied by using strains with lacZ fused to their respective promoters. psiE-lacZ is induced by phosphate-, carbon- or nitrogen-limited growth. Genetically, psiE-lacZ induction is partially phoB and phoR-dependent. However, its expression is phoM-independent. This implies that phoB/phoR coupled control differs from phoB/phoM coupled control. Repression of psiE-lacZ is substantially altered in only some PST mutants, such as phoT. In addition, psiE-lacZ is negatively controlled by the cAMP and CAP system. psiO-lacZ is induced by phosphate-, carbon- or nitrogen-limited growth or by anaerobiosis. Its expression is unaffected by any pho mutation that has been previously described. A cell density-dependent induction of psiO-lacZ is observed in lon mutants. Also, psiO-lacZ is negatively controlled by the cAMP-CAP system. In summary, these results demonstrate that co-ordinately regulated promoters can have some common regulatory elements while, at the same time, not sharing other controlling factors.
J Mol Biol 1983 May 25
PMID:Overlapping and separate controls on the phosphate regulon in Escherichia coli K12. 630 24

Two mitochondrially synthesized marker polypeptides, MV-1 and MV-2, were found in human HeLa and HT1080 cells. These were assigned to the mitochondrial DNA in HeLa-HT1080 cybrids and hybrids by demonstrating their linkage to cytoplasmic genetic markers. These markers include mitochondrial DNA restriction site polymorphisms and resistance to chloramphenicol, an inhibitor of mitochondrial protein synthesis. In the absence of chloramphenicol, the expression of MV-1 and MV-2 in cybrids and hybrids was found to be directly proportional to the ratio of the parental mitochondrial DNAs. In the presence of chloramphenicol, the marker polypeptide linked to the chloramphenicol-sensitive mitochondrial DNA continued to be expressed. This demonstrated that resistant and sensitive mitochondrial DNAs can cooperate within a cell for gene expression and that the CAP-resistant allele was dominant or codominant to sensitive. Such cooperation suggests that mitochondrial DNAs can be exchanged between mitochondria.
Mol Cell Biol 1982 Jan
PMID:Assignment of two mitochondrially synthesized polypeptides to human mitochondrial DNA and their use in the study of intracellular mitochondrial interaction. 695 89

Expression of human prostatic acid phosphatase (ACPP) and prostate specific antigen (PSA) genes in prostatic carcinoma (CAP) and benign prostatic hyperplasia (BPH) was investigated by northern blot analyses. The expressions of ACPP and PSA, as well as the glycolytic enzymes glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase-muscle (LDH-A), were elevated significantly in prostatic carcinoma when compared with the expressions of these genes in benign prostatic hyperplasia in the same patient. The expression of the actin gene in both neoplastic and benign hyperplasia remained the same.
Biochem Mol Biol Int 1994 Jun
PMID:Expression of human prostatic acid phosphatase and prostate specific antigen genes in neoplastic and benign tissues. 752 3

The c-myc oncogene c-Myc is commonly activated in cancer and transactivates gene expression by binding to CACGTG DNA sequences as a heterodimeric complex with Max. The ornithine decarboxylase (ODC), p53, prothymosin alpha and ECA39 promoters are transactivated by c-Myc, and are considered direct targets, as activation is mediated by CACGTG sequences. Interestingly, the c-Myc-responsive CACGTG sequences in the p53, prothymosin alpha, ECA39 and murine ODC genes are all downstream of the RNA CAP site, suggesting that downstream sequences are preferred c-Myc targets. Using a series of heterologous reporter constructs, we have tested the effects of position and orientation of c-Myc-responsive CACGTG sequences on c-Myc's ability to activate transcription. A single binding site conferred c-Myc-responsiveness independent of position and orientation, and over distances of 1.7 kbp. The extent of transactivation was not significantly influenced by position of the responsive elements. By contrast, the extent of transactivation was dependent upon the number of c-Myc binding sites. The results demonstrate that c-Myc activates transcription independent of position and orientation and that considerable flexibility exists in the interaction of c-Myc transactivation domains with the general transcription machinery.
Cell Mol Biol Res 1994
PMID:Position and orientation independent transactivation by c-Myc. 778 88

The NagC repressor binds to two sites in the intergenic nagE-B region overlapping the divergently expressed nagE and nagB promoters. In addition the NagC repressor binds to two sites upstream of the manXYZ operon. Although basically palindromic, there is little sequence consensus between the four operators. To identify the DNA sequence important for NagC recognition, we have taken advantage of the fact that repression of the nagE and nagB genes requires the formation of a loop of DNA between molecules of the repressor bound to the nagE and nagB operators. The nagE operator was systematically mutagenised and the effect of the mutations measured on the level of expression from a nagB-lacZ fusion. These experiments showed that the most important positions for recognition are the two A.T base-pairs at positions-5 and -6 from the centre of symmetry. These are the only absolutely conserved bases in the four operators. Certain changes of residues at position -3 and -4 have fairly strong effects while changes at -7 to -10 have only minor effects. However the presence of a G or C base at positions + 11 or -11 produces a NagC binding site with considerably higher affinity than the wide-type nagE operator both in vitro and in vivo, a "super-operator". The presence of a super-operator considerably increased the stability of the binary looped NagC-DNA complex in vitro. However in the presence of cAMP/CAP, NagC showed the same apparent binding affinity to wild-type and super-operators indicating that one role of cAMP/CAP in the repression complex is to reduce the need for high affinity sites. These super-operators allow a higher level of repression of the nagE promoter compared to the nagB, presumably due to the existence of linear complexes of NagC bound to BoxE.
J Mol Biol 1995 Jun 23
PMID:Nag repressor-operator interactions: protein-DNA contacts cover more than two turns of the DNA helix. 779 Dec 15

The res sites, the loci for site-specific recombination by resolvase, contain three binding sites for the protein; the cross-over site, I, and accessory sites II and III. The role of DNA bending by resolvase was examined by replacing either II or III in the res site from Tn21 with the recognition sequence for a heterologous DNA-bending protein, CAP (the catabolite-gene activator protein from Escherichia coli). The CAP sequence was placed at either the same position as the target sequence for Tn21 resolvase or a different position along the DNA. The activity of Tn21 resolvase for recombination between each hybrid and a wild-type res site was measured in the presence of CAP and cyclic AMP. When III was substituted, CAP inhibited Tn21 recombination, except when the CAP sequence was placed sufficiently far away from site II to allow resolvase to bind non-specifically to the DNA between II and the CAP site. With the substitutions at II, the extent of Tn21 recombination in the presence of CAP varied with the position of the CAP sequence: more recombination was observed when it superimposed the target sequence for resolvase than when it was displaced by five base-pairs. Efficient recombination by Tn21 resolvase thus seems to demand the cognate protein at site III in res, presumably for protein-protein interactions in the synaptic complex, while the function of resolvase at site II can be fulfilled, at least in part, by a heterologous DNA bend.
J Mol Biol 1995 Jan 20
PMID:Site-specific recombination at res sites containing DNA-binding sequences for both Tn21 resolvase and CAP. 784 14

Hepatocyte growth factor (HGF), a cytokine with multiple functions, exhibits cell-type-specific as well as cytokine- and steroid hormone-regulated expression. The HGF gene is known to be expressed predominately in mesenchymal but not in epithelial cells. In this study, we report the identification of a cell-type-specific transcriptional repressor in the promoter region of the mouse HGF gene, which is evidently responsible for the suppression of HGF expression in epithelial cells. Gel mobility shift assays and DNase I footprinting studies revealed that a 27-bp element (-16 to +11) around the transcription initiation site is responsible for the binding of a nuclear protein which is present in epithelial but not in mesenchymally derived cells. Further analysis of the binding activity of the DNA region with nuclear protein revealed that an approximately 19-bp sequence containing a unique palindromic structure (5'-AACCGACCGGTT-3') overlapped by a CAP box is essential for binding. Substitution of a single base (the contact site) within this region by site-directed mutagenesis resulted in total abrogation of the binding of the nuclear protein and a concomitant increase in the transcriptional activity of various lengths of HGF-chloramphenicol acetyltransferase fused genes when transfected into the epithelial cell line RL95-2 but not the mesenchymal cell line NIH 3T3. Southwestern (DNA-protein) analyses revealed that the nuclear protein which binds to this repressor element is a single polypeptide of approximately 70 kDa. Analysis of the nuclear extract prepared from regenerating mouse liver at various times after two-thirds partial hepatectomy by gel mobility shift assay revealed a substantial reduction (more than 75% within 3 h) in the binding of the repressor to its cognate binding site. Our results suggest that a cis-acting transcriptional repressor in the promoter region of the mouse HGF gene is involved in cell-type-specific regulation through binding to its cognate trans-acting protein which exists in epithelial cells but is absent in fibroblast cells.
Mol Cell Biol 1994 Nov
PMID:Identification of a cell-type-specific transcriptional repressor in the promoter region of the mouse hepatocyte growth factor gene. 793 20

CAP-dependent promoters can be divided into classes based on the position of the DNA site for CAP. In class I CAP-dependent promoters, the DNA site for CAP is located upstream of the DNA site for polymerase; the DNA site for CAP can be located at various distances from the transcription start point, provided that the DNS site for CAP and the DNA site for RNA polymerase are on the same face of the DNA helix. In class II CAP-dependent promoters, the DNA site for CAP overlaps the DNA site for RNA polymerase, replacing the -35 determinants for binding of RNA polymerase. In previous work, we have shown that a surface loop consisting of amino acid residues 152 to 166 of CAP is essential for transcription activation at the best-characterized class I CAP-dependent promoter, the lac promoter, and we proposed that this surface loop makes direct protein-protein contact with RNA polymerase in the ternary complex of lac promoter, CAP, and RNA polymerase. Here, we show that the surface loop consisting of amino acid residues 152 to 166 is essential for transcription activation at other class I CAP-dependent promoters and at a class II CAP-dependent promoter. We show further that the effects of alanine substitutions of residues 152 to 166 are qualitatively identical at the lac promoter and other class I CAP-dependent promoters, but are different at a class II CAP-dependent promoter. We propose that the surface loop consisting of residues 152 to 166 makes identical molecular interactions in transcription activation at all class I CAP-dependent promoters, irrespective of distance between the DNA site for CAP and the transcription start point, but makes a different set of molecular interactions in transcription activation at class II CAP-dependent promoters.
J Mol Biol 1994 Nov 04
PMID:Characterization of the activating region of Escherichia coli catabolite gene activator protein (CAP). II. Role at Class I and class II CAP-dependent promoters. 796 85

Heteronuclear multidimensional NMR experiments of residues 33-163 of the DNA-binding domain of Drosophila heat shock factor, dHSF(33-163), were recorded, using only 3 mg of uniformly 15N-labeled or 2 mg of uniformly 15N/13C-labeled protein. The polypeptide consists of a structured part comprising three helices, a three-stranded antiparallel beta-sheet, with the first two strands connected by a four-residue type I tight turn. The second helix is disrupted at its C-terminal end by a proline residue and is followed by an extended turn, leading to the third helix. The dHSF(33-163) protein is unstructured at its N- and C-termini, and a third unstructured region is found from Thr113 to Arg124. Exchange broadening of the 15N-1H correlations upon titration of 15N labeled HSF with a 13-base-pair DNA duplex suggests a DNA-binding motif in which the third helix acts as the recognition helix. Both the secondary structure and DNA-binding pattern of dHSF(33-163) suggest that the overall topology resembles that the helix-turn-helix bacterial activator CAP [Weber, I. T., & Steitz, T. A. (1987) J. Mol. Biol. 198, 311-326] and the liver-specific transcription factor HNF-3 gamma, the prototype of the HNF-3/forkhead protein family [Clark, K. L., Halay, E. D., Lai, E., & Burley, S. K. (1993) Nature 364, 412-420].
 ...
PMID:NMR evidence for similarities between the DNA-binding regions of Drosophila melanogaster heat shock factor and the helix-turn-helix and HNF-3/forkhead families of transcription factors. 828 26

In arterial hypertension associated with primary or secondary hyperaldosteronism myocardial fibrosis is an important determinant of pathologic hypertrophy. To further examine the relationship between elevations in plasma aldosterone (ALDO) and myocardial fibrosis, we analysed perivascular collagen area (PVCA) and interstitial collagen volume fraction (CVF) by videodensitometry and hydroxyproline concentration (HPro) by high-performance liquid chromatography. We examined both the left (LV) and right (RV) ventricles in the following rats models of primary or secondary hyperaldosteronism of eight weeks duration: unilateral renal ischemia (RHT); continuous ALDO administration via osmotic minipumps (0.75 microgram/h s.c.) and enhanced dietary sodium following uninephrectomy (AL); in RHT and AL after pre- and continuous treatment with either 20 (S) or 200 (SS) mg/kg/day s.c. of the aldosterone receptor antagonist, spironolactone; in AL after pre- and continuous treatment with 50 mg/kg/day oral captopril (AL + CAP); as well as in age and sex matched controls (C). Systolic arterial pressure was comparably elevated in RHT and AL (202 +/- 12 and 193 +/- 7 mmHg, respectively; P < 0.0005 vs C); it remained elevated with low dose spironolactone in either model of arterial hypertension, but was normalized with high dose spironolactone or captopril in AL. Left ventricular hypertrophy (LVH), expressed as significantly elevated LV/RV weight or LV/BW ratios, was present in all experimental groups, excluding AL + SS and AL + CAP, when compared with C (P < 0.005). In each ventricle, CVF and PVCA were increased (P < 0.005) in either model of hypertension and in AL + CAP, but were no different from C in all groups receiving either dose of spironolactone. Similar findings were observed for HPro. Thus, myocardial fibrosis was comparable in primary or secondary hyperaldosteronism, wherein elevations in plasma aldosterone, relative to increased sodium intake, are associated with arterial hypertension. The competitive ALDO receptor antagonist, spironolactone, was able to prevent fibrosis in either model irrespective of the development of LVH and the presence of hypertension. Captopril prevented hypertension and LVH, but not unexpectedly it did not prevent myocardial fibrosis in primary hyperaldosteronism. These findings provide further evidence that in these rat models increased plasma ALDO, relative to dietary sodium, plays a major role in the adverse accumulation of collagen that appears in the myocardium.
J Mol Cell Cardiol 1993 May
PMID:Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. 837 16


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