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Query: UNIPROT:P06889 (Mol)
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The LexA repressor controls the expression of several SOS genes, such as lexA, recA and sfiA, which are induced by DNA damage. Induction results from the activation of the RecA protein that favours the cleavage and thus the inactivation of LexA. It has been shown that the activation of RecA results from its binding to damaged DNA. It is therefore believed that in growing bacteria, in the absence of any DNA-damaging treatment, the intracellular level of LexA remains stable at a high basal level and, hence, SOS genes are expressed at relatively low basal levels. In contrast, we show here that the intracellular level of LexA and the rate of transcription of the sfiA gene may vary markedly throughout the growth cycle of wild-type Escherichia coli. We provide evidence that such changes result from two superimposed processes: proteolytic cleavage of LexA upon dilution of stationary phase bacteria, and increase in strength of the promoters of the lexA and sfiA genes when bacteria approach the stationary phase. We show that a signal which strongly increases the strength of the sfiA gene promoter is starvation for phosphate. Such induction was not significantly affected by mutations either in phoB (encoding the transcriptional regulator for the phosphate regulon) or rpoS (encoding a putative stationary phase-specific sigma factor). However, sfiA induction by phosphate starvation appeared to be markedly inhibited by the presence of the osmZ205 mutation which alters the histone-like protein H-NS, suggesting that changes in the DNA structure may play a role in signal transduction during phosphate starvation. As previously shown for several processes which are controlled by H-NS, induction of sfiA was modulated by growth temperature.
Mol Microbiol 1993 May
PMID:Phosphate starvation and low temperature as well as ultraviolet irradiation transcriptionally induce the Escherichia coli LexA-controlled gene sfiA. 833 62

The expression of the Rhizobium meliloti C4-dicarboxylic acid permease gene (dctA) is controlled by the sensor DctB and the transcriptional regulator, DctD. The R. meliloti Dct system has been reconstituted in Escherichia coli. Expression of the dctA promoter is DctBD dependent and is induced in the presence of C4-dicarboxylic acids (dCA). Other carbon sources also influence dctA expression. We demonstrate that the cAMP receptor protein (CRP) has a repressive effect on the dctA promoter. A mutated CRP molecule (CRP-H159L), unable to activate catabolic promoters (but still proficient in DNA binding), gives similar results. This suggests that the CRP-cAMP complex represses the dctA promoter activity by direct interaction with the DNA. Direct binding of the CRP-cAMP complex to the dctA promoter was confirmed in vitro by gel mobility-shift assays. Sequence analysis of the dctA promoter indicates that the most likely binding sites for CRP are the two confirmed DctD-binding sites. It is proposed that the CRP-cAMP complex competes with DctD for occupancy of these sites. Since in the presence of CRP-cAMP complex the uninduced levels of dctA expression are reduced, whereas induced levels are largely unaffected, such competition appears to be an essential regulatory feature of dctA expression.
Mol Microbiol 1993 Apr
PMID:The Escherichia coli cAMP receptor protein (CRP) represses the Rhizobium meliloti dctA promoter in a cAMP-dependent fashion. 839 Nov 3

MRF4 is a member of the muscle-specific basic helix-loop-helix transcription factor family that also includes MyoD, myogenin, and Myf-5. Each of these proteins, when overexpressed in fibroblasts, converts the cells to differentiated muscle fibers that express several skeletal muscle genes, such as those for alpha-actin, muscle creatine kinase, and troponin I. Despite the fact that MRF4 functions as a positive transcriptional regulator, the MRF4 protein is subject to negative regulation by a variety of agents, most notably by exposure of cells to purified growth factors, such as basic fibroblast growth factor (bFGF). In an effort to establish whether bFGF inhibits MRF4 activity through specific posttranslational modifications, we examined whether MRF4 exists in vivo as a phosphoprotein and whether the phosphorylation status of the protein regulates its activity. Our results indicate that MRF4 is phosphorylated predominantly on serine residues, with weak phosphorylation occurring on threonine residues. Both cyclic AMP-dependent protein kinase (PKA) and protein kinase C (PKC) phosphorylate MRF4 in vitro as well as in vivo, and the overexpression of each kinase inhibits MRF4 activity and thus blocks terminal differentiation. PKC-directed phosphorylation of a conserved threonine residue (T-99) situated within the DNA-binding domain inhibits MRF4 from binding in vitro to specific DNA targets. However, although T-99 itself is essential for myogenic activity, our studies demonstrate that the phosphorylation status of T-99 does not play a major role in regulating MRF4 activity in vivo, since PKA, PKC, and bFGF inhibit the activity of MRF4 proteins in which the identified PKA and PKC sites have been mutated. We suggest that the negative regulation of MRF4 imposed by bFGF does not involve a direct modification of the protein at the identified PKA and PKC sites but instead may involve the modification of specific coregulators that interact with this muscle regulatory factor.
Mol Cell Biol 1993 Oct
PMID:Fibroblast growth factor inhibits MRF4 activity independently of the phosphorylation status of a conserved threonine residue within the DNA-binding domain. 841 99

The Escherichia coli nucleoid protein, H-NS (or H1a), appears to influence the regulation of a variety of unrelated E. coli genes and operons. To gain an insight into the regulation of the hns gene itself, we constructed in this study a hns-lacZ transcriptional fusion gene and inserted a single copy at the att lambda locus on the E. coli chromosome. Expression of hns transcription appeared to be moderately regulated in a growth phase-dependent manner. It also emerged that hns transcription is under negative autoregulation, at least in the logarithmic growth phase. The results of in vitro transcription experiments confirmed that H-NS functions as a repressor for its own transcription. Thus, H-NS was shown to exhibit relatively high affinity for the DNA sequence encompassing the hns promoter region, as compared with a non-specific sequence. These results support the view that the nucleoid protein, H-NS, can function as a transcriptional regulator.
Mol Gen Genet 1993 Jan
PMID:Autoregulatory expression of the Escherichia coli hns gene encoding a nucleoid protein: H-NS functions as a repressor of its own transcription. 843 61

The yeast SIN3 gene (also known as SDI1, UME4, RPD1, and GAM2) has been identified as a transcriptional regulator. Previous work has led to the suggestion that SIN3 regulates transcription via interactions with DNA-binding proteins. Although the SIN3 protein is located in the nucleus, it does not bind directly to DNA in vitro. We have expressed a LexA-SIN3 fusion protein in Saccharomyces cerevisiae and show that this fusion protein represses transcription from heterologous promoters that contain lexA operators. The predicted amino acid sequence of the SIN3 protein contains four copies of a paired amphipathic helix (PAH) motif, similar to motifs found in HLH (helix-loop-helix) and TPR (tetratricopeptide repeat) proteins, and these motifs are proposed to be involved in protein-protein interactions. We have conducted a deletion analysis of the SIN3 gene and show that the PAH motifs are required for SIN3 activity. Additionally, the C-terminal region of the SIN3 protein is sufficient for repression activity in a LexA-SIN3 fusion, and deletion of a PAH motif in this region inactivates this repression activity. A model is presented in which SIN3 recognizes specific DNA-binding proteins in vivo in order to repress transcription.
Mol Cell Biol 1993 Mar
PMID:Transcriptional repression in Saccharomyces cerevisiae by a SIN3-LexA fusion protein. 844 14

Rev-ErbA alpha (Rev-Erb) is a nuclear hormone receptor-related protein encoded on the opposite strand of the alpha-thyroid hormone receptor (TR) gene. This unusual genomic arrangement may have a regulatory role, but the conservation of human and rodent Rev-Erb amino acid sequences suggests that the protein itself has an important function, potentially as a sequence-specific transcriptional regulator. However, despite its relationship to the TR, Rev-Erb bound poorly to TR binding sites. To determine its DNA-binding specificity in an unbiased manner, Rev-Erb was synthesized in Escherichia coli, purified, and used to select specific binding-sites from libraries of random double-stranded DNA sequences. We found that Rev-Erb binds to a unique site consisting of a specific 5-bp A/T-rich sequence adjacent to a TR half-site. Rev-Erb contacts this entire asymmetric 11-bp sequence, which is the longest nonrepetitive element specifically recognized by a member of the thyroid/steroid hormone receptor superfamily, and mutations in either the A/T-rich or TR half-site regions abolished specific binding. The binding specificity of wild-type Rev-Erb was nearly identical to that of C- and N-terminally truncated forms. This binding was not enhanced by retinoid X receptor, TR, or other nuclear proteins, none of which formed heterodimers with Rev-Erb. Rev-Erb also appeared to bind to the selected site as a monomer. Furthermore, Rev-Erb activates transcription through this binding site even in the absence of exogenous ligand. Thus, Rev-Erb is a transcriptional activator whose properties differ dramatically from those of classical nuclear hormone receptors, including the TR encoded on the opposite strand of the same genomic locus.
Mol Cell Biol 1993 May
PMID:The orphan receptor Rev-ErbA alpha activates transcription via a novel response element. 847 64

Spo0A is a positive/negative transcriptional regulator that plays a very important role in sporulation initiation in Bacillus subtilis. The N-terminal amino acid sequence of Spo0A is homologous to that of regulator proteins of the two-component regulatory systems involved in signal transduction in bacteria. Phosphorylation of SpooA through a phosphorelay has been reported recently. In this study, we found that Spo0A is autophosphorylated in the presence of ATP and that an autophosphorylation-deficient Spo0A mutant is completely defective in initiating sporulation. These results suggest that Spo0A autophosphorylation is an essential event in the signal transduction process that controls sporulation in B. subtilis.
Mol Gen Genet 1993 Apr
PMID:Signal transduction and sporulation in Bacillus subtilis: autophosphorylation of Spo0A, a sporulation initiation gene product. 847 20

Synthesis of urease by Klebsiella species is known to be induced when the nitrogen source of the growth medium is limiting, suggesting that urease gene expression is controlled by the nitrogen regulatory (ntr) system. This study showed that K. pneumoniae with mutations in either ntrA or ntrC, two integral components of the ntr system, were phenotypically urease-negative. These mutants could be complemented back to a urease positive phenotype with recombinant plasmids encoding the corresponding ntr gene. A series of ure-lacZYA transcriptional fusions, in conjunction with primer extension analysis, identified a DNA region that encoded a nitrogen-regulated promoter. This promoter region controlled transcription of ureD, the first gene in the Klebsiella pneumoniae urease gene cluster, and ureA, a gene that resides immediately downstream of ureD. A high level of transcription from the ureD promoter required NAC, a recently characterized member of the nitrogen regulatory cascade. NAC is a Lys R-like transcriptional regulator that can act at sigma 70 promoters; expression from nac itself is dependent upon NTRA. Therefore, expression of K. pneumoniae urease was dependent upon the nitrogen regulatory cascade, and transcription of at least two urease genes was from a promoter that was positively regulated by NAC.
Mol Microbiol 1993 Apr
PMID:Identification of a nitrogen-regulated promoter controlling expression of Klebsiella pneumoniae urease genes. 849 92

FNR is a transcriptional regulator controlling the expression of a number of Escherichia coli genes in response to anoxia. It is structurally-related to CRP (the cyclic AMP receptor protein) except for the presence of a cysteine-rich N-terminal extension, which may form part of an iron-binding, redox-sensing domain in FNR. Site-directed substitution has previously shown that four of the cysteine residues (C20, C23, C29 and C122) are essential for FNR function, whereas the fifth (C16) is not. The FNR protein exists in two forms separable by non-reducing SDS-PAGE, and in studies with altered FNR proteins containing single substitutions at each of the five cysteine residues it was concluded that the faster-migrating form (FNR(27)), possesses an intramolecular disulphide bond linking C122 to one of the cysteines near the N-terminus. FNR(27) was more abundant in aerobic cells but the physiological significance of this was not established. Footprint studies indicated that FNR proteins lacking essential cysteine residues are impaired in their ability to protect FNR sites in the ndh promoter. The non-essential cysteine residue (C16) was identified as the source of the most reactive sulphydryl group and all of the inactive proteins exhibited different sulphydryl reactivities. The iron content of the C122A-substituted protein was much reduced but those of the other proteins were less affected. Electrospray mass spectrometry confirmed the accuracy of the gene-derived amino acid composition of FNR with a mutant protein and it showed that a fraction of the wild-type protein may carry a 78 Da substituent which could not be removed with dithiothreitol or beta-mercaptoethanol.
Mol Microbiol 1993 Apr
PMID:Properties of FNR proteins substituted at each of the five cysteine residues. 849 98

The Achaete (Ac) protein, a transcriptional regulator of the basic-helix-loop-helix (bHLH) type, confers upon ectodermal cells the ability to become neural precursors. Its temporally and spatially regulated expression, together with that of the related Scute (Sc) protein, helps define the pattern of Drosophila melanogaster sensory organs. We have examined the transcriptional control of the ac gene and shown, using in vivo assays, that several E-boxes, putative interacting sites for bHLH proteins, present in the ac promoter are most important for ac regulation. They most likely mediate ac self-stimulation and sc trans-activation. We also demonstrate that ac transcription is negatively regulated in vivo by the gene extramacrochaetae (emc) in a manner dependent on Ac and Sc products. emc encodes an HLH protein that lacks the basic region and presumably antagonizes Ac and Sc function by sequestering these proteins in complexes unable to interact with DNA. Our results strongly support the model of negative regulation of emc on ac and sc transcription through titration of their products. As currently thought, this seems accomplished by heterodimerization via the HLH domain, because an amino acid substitution in this region abolishes the emc antagonistic effect both in vitro and in vivo.
Mol Cell Biol 1993 Jun
PMID:Regulation of the proneural gene achaete by helix-loop-helix proteins. 849 66


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