UNIPROT:P51532 - FACTA Search

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Query: UNIPROT:P51532 (transcriptional activator)
6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Gal system of Saccharomyces cerevisiae is a paradigm for eukaryotic gene regulation. Expression of genes required for growth on galactose is regulated by the transcriptional activator Gal4. The activation function of Gal4 has been localized to 34 amino acids near the C terminus of the protein. The gal4D allele of GAL4 encodes a truncated protein in which only 14 amino acids of the activation domain remain. Expression of GAL genes is dramatically reduced in gal4D strains and these strains are unable to grow on galactose as the sole carbon source. Overexpression of gal4D partially relieves the defect in GAL gene expression and allows growth on galactose. A search for extragenic suppressors of gal4D identified recessive mutations in the SUG1 and SUG2 genes, which encode ATPases of the 19S regulatory complex of the proteasome. The proteasome is responsible for the ATP-dependent degradation of proteins marked for destruction by the ubiquitin system. It has been commonly assumed that effects of SUG1 and SUG2 mutations on transcription are explained by alterations in the proteolysis of gal4D protein. We have investigated this assumption. Surprisingly, we find that SUG1 and SUG2 alleles that are unable to suppress gal4D cause a larger increase in gal4D protein levels than do suppressing alleles. In addition, mutations in genes encoding subunits of the proteolytic 20S sub-complex of the proteasome increase the levels of gal4D protein but do not rescue its transcriptional activity. Therefore, an alteration in the proteolysis of gal4D by the proteasome cannot explain the effects of mutations in SUG1 and SUG2 on expression of GAL genes. These findings suggest that the 19S regulatory complex may play a more direct role in transcription.
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PMID:Evidence that proteolysis of Gal4 cannot explain the transcriptional effects of proteasome ATPase mutations. 1115 78

Flagellar number in Pseudomonas aeruginosa is controlled by FleN, a putative ATP/GTP binding protein. Disruption of fleN results in multiflagellation of the otherwise monoflagellate strains PAK and PAO1 and is associated with a chemotactic defect. We propose that flagellar number is maintained by the antiactivator FleN, which downregulates flagellar genes by binding to their transcriptional activator, FleQ, an enhancer binding protein belonging to the NifA subfamily. In this report we demonstrate direct interaction of FleN and FleQ in the yeast two-hybrid system. Mutagenesis of the putative ATP/GTP binding motif in FleN(24K-->Q) and truncation of FleN at either the N or C terminus abrogates this interaction. FleN does not inhibit the DNA binding ability of FleQ in vitro, thus indicating that it probably utilizes another mechanism(s) to serve as a FleQ antiactivator.
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PMID:Interaction of the antiactivator FleN with the transcriptional activator FleQ regulates flagellar number in Pseudomonas aeruginosa. 1167 34

MalT, the transcriptional activator of the maltose regulon from Escherichia coli, is the prototype of a new family of transcription factors. Its activity is controlled by multiple regulatory signals. ATP and maltotriose (the inducer) are two effectors of the activator that positively control its multimerization, a critical step in promoter binding. In addition, MalK, the ABC component of the maltodextrin transport system, and the two enzymes MalY and Aes down-regulate MalT activity in vivo. By using a biochemical approach, we demonstrate here that (i) Aes controls MalT activity through direct protein-protein interaction, (ii) Aes competes with maltotriose for MalT binding, (iii) ATP and ADP differentially affect the competition between Aes and the inducer, and (iv) part, if not all, of the Aes binding site is located in DT1, the N-terminal domain of the activator, which also contains the ATP binding site. All of these characteristics point toward an identical mode of action for MalY and Aes. However, we have identified an amino acid substitution in MalT that suppresses MalT inhibition by Aes without interfering with its inhibition by MalY, suggesting that the binding sites of the two inhibitory proteins do not coincide. The differential effects of ATP and ADP on the competition between the inducer and Aes (or MalY) suggest that the ATPase activity displayed by MalT plays a role in the negative control of its activity.
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PMID:The Aes protein directly controls the activity of MalT, the central transcriptional activator of the Escherichia coli maltose regulon. 1186 39

The enzymatic reduction of molecular nitrogen to ammonia requires high amounts of energy, and the presence of oxygen causes the catalyzing nitrogenase complex to be irreversible inactivated. Thus nitrogen-fixing microorganisms tightly control both the synthesis and activity of nitrogenase to avoid the unnecessary consumption of energy. In the free-living diazotrophs Klebsiella pneumoniae and Azotobacter vinelandii, products of the nitrogen fixation nifLA operon regulate transcription of the other nifoperons. NifA activates transcription of nif genes by the alternative form of RNA-polymerase, sigma54-holoenzyme; NifL modulates the activity of the transcriptional activator NifA in response to the presence of combined nitrogen and molecular oxygen. The translationally-coupled synthesis of the two regulatory proteins, in addition to evidence from studies of NifL/NifA complex formation, imply that the inhibition of NifA activity by NifL occurs via direct protein-protein interaction in vivo. The inhibitory function of the negative regulator NifL appears to lie in the C-terminal domain, whereas the N-terminal domain binds FAD as a redox-sensitive cofactor, which is required for signal transduction of the internal oxygen status. Recently it was shown, that NifL acts as a redox-sensitive regulatory protein, which modulates NifA activity in response to the redox-state of its FAD cofactor, and allows NifA activity only in the absence of oxygen. In K. pneumoniae, the primary oxygen sensor appears to be Fnr (fumarate nitrate reduction regulator), which is presumed to transduce the signal of anaerobiosis towards NifL by activating the transcription of gene(s) whose product(s) function to relieve NifL inhibition through reduction of the FAD cofactor. In contrast, the reduction of A. vinelandii-NifL appears to occur unspecifically in response to the availability of reducing equivalents in the cell. Nitrogen status of the cells is transduced towards the NifL/NifA regulatory system by the GlnK protein, a paralogue PII-protein, which appears to interact with the NifL/NifA regulatory system via direct protein-protein interaction. It is not currently known whether GlnK interacts with NifL alone or affects the NifL/NifA-complex; moreover the effects appear to be the opposite in K. pneumoniae and A. vinelandii. In addition to these environmental signals, adenine nucleotides also affect the inhibitory function of NifL; in the presence of ATP or ADP the inhibitory effect on NifA activity in vitro is increased. The NifL proteins from the two organisms differ, however, in that stimulation of K. pneumoniae-NifL occurs only when synthesized under nitrogen excess, and is correlated with the ability to hydrolyze ATP. In general, transduction of environmental signals to the nif regulatory system appears to involve a conformational change of NifL or the NifL/NifA complex. However, experimental data suggest that K. pneumoniae and A. vinelandii employ significantly different species-specific mechanisms of signal transduction.
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PMID:Regulation of nitrogen fixation in Klebsiella pneumoniae and Azotobacter vinelandii: NifL, transducing two environmental signals to the nif transcriptional activator NifA. 1193 53

The genes of the Escherichia coli maltose regulon are controlled by MalT, the specific transcriptional activator which, together with the inducer maltotriose and ATP, is essential for mal gene transcription. Network regulation in this system affects the function of MalT and occurs on two levels. The first concerns the expression of malT. It has long been known that malT is under catabolite repression and thus under the control of the cAMP/CAP complex. We found that, in addition, the global regulator Mlc is a repressor for malT transcription. The repressor activity of Mlc is controlled by the transport status of the glucose-specific enzyme EIICB of the PTS that causes sequestration (and inactivation as a repressor) of Mlc when glucose is transported. The second level of MalT regulation affects its activity. MalT is activated by maltotriose which is not only formed when the cells are growing on any maltodextrin but also, in low amounts, endogenously when the cells grow on non-maltodextrin carbon sources. Thus, cellular metabolism, for instance degradation of galactose or trehalose, can cause mal gene induction. It was found that unphosphorylated internal glucose takes part in endogenous maltodextrin biosynthesis and is therefore a key element in endogenous mal gene expression. In addition to the maltotriose-dependent activation, MalT can interact with three different enzymes that lead to its inactivation as a transcriptional activator. The first is MaIK, the energy transducing ABC subunit of the maltodextrin transport system. Transport controls the interaction of MalK and MalT thus affecting gene expression. The second enzyme is MalY, a pyridoxal phosphate containing enzyme exhibiting cystathionase activity. The crystal structure of MalY was established and mutations in MalY that reduce mal gene repression map in a hydrophobic MalT interaction patch on the surface of the enzyme. The last enzyme is a soluble esterase of as yet unknown function. When overproduced, this enzyme specifically reduces mal gene expression and affects the activity of MalT in an in vitro transcription assay.
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PMID:Network regulation of the Escherichia coli maltose system. 1193 62

AfsR is a pleiotropic, global regulator that controls the production of actinorhodin, undecylprodigiosin and calcium-dependent antibiotic in Streptomyces coelicolor A3(2). AfsR, with 993 amino acids, is phosphorylated on serine and threonine residues by a protein serine/threonine kinase AfsK and contains an OmpR-like DNA-binding fold at its N-terminal portion and A- and B-type nucleotide-binding motifs in the middle of the protein. The DNA-binding domain, in-dependently of the nucleotide-binding domain, contributed the binding of AfsR to the upstream region of afsS that locates immediately 3' to afsR and encodes a 63-amino-acid protein. No transcription of afsS in the DeltaafsR background and restoration of afsS transcription by afsR on a plasmid in the same genetic background indicated that afsR served as a transcriptional activator for afsS. Interestingly, the AfsR binding site overlapped the promoter of afsS, as determined by DNase I protection assay and high-resolution S1 nuclease mapping. The nucleotide-binding domain contributed distinct ATPase and GTPase activity. The phosphorylation of AfsR by AfsK greatly enhanced the DNA-binding activity and modulated the ATPase activity. The DNA-binding ability of AfsR was independent of the ATPase activity. However, the ATPase activity was essential for transcriptional activation of afsS, probably because the energy available from ATP hydrolysis is required for the isomerization of the closed complex between AfsR and RNA polymerase to a transcriptionally competent open complex. Thus, AfsR turns out to be a unique transcriptional factor, in that it is modular, in which DNA-binding and ATPase activities are physically separable, and the two functions are modulated by phosphorylation on serine and threonine residues.
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PMID:afsS is a target of AfsR, a transcriptional factor with ATPase activity that globally controls secondary metabolism in Streptomyces coelicolor A3(2). 1195 95

The genes encoding the enzymes required for galactose metabolism in Saccharomyces cerevisiae are controlled at the level of transcription by a genetic switch consisting of three proteins: a transcriptional activator, Gal4p; a transcriptional repressor, Gal80p; and a ligand sensor, Gal3p. The switch is turned on in the presence of two small molecule ligands, galactose and ATP. Gal3p shows a high degree of sequence identity with Gal1p, the yeast galactokinase. We have mapped the interaction between Gal80p and Gal3p, which only occurs in the presence of both ligands, using protease protection experiments and have shown that this involves amino acid residue 331 of Gal80p. Gel-filtration experiments indicate that Gal3p, or the galactokinase Gal1p, interact directly with Gal80p to form a complex with 1:1 stoichiometry.
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PMID:Gal3p and Gal1p interact with the transcriptional repressor Gal80p to form a complex of 1:1 stoichiometry. 1196 51

Acetone carboxylase is the key enzyme of bacterial acetone metabolism, catalyzing the condensation of acetone and CO(2) to form acetoacetate. In this study, the acetone carboxylase of the purple nonsulfur photosynthetic bacterium Rhodobacter capsulatus was purified to homogeneity and compared to that of Xanthobacter autotrophicus strain Py2, the only other organism from which an acetone carboxylase has been purified. The biochemical properties of the enzymes were virtually indistinguishable, with identical subunit compositions (alpha(2)beta(2)gamma(2) multimers of 85-, 78-, and 20-kDa subunits), reaction stoichiometries (CH(3)COCH(3) + CO(2) + ATP-->CH(3)COCH(2)COO(-) + H(+) + AMP + 2P(i)), and kinetic properties (K(m) for acetone, 8 microM; k(cat) = 45 min(-1)). Both enzymes were expressed to high levels (17 to 25% of soluble protein) in cells grown with acetone as the carbon source but were not present at detectable levels in cells grown with other carbon sources. The genes encoding the acetone carboxylase subunits were identified by transposon mutagenesis of X. autotrophicus and sequence analysis of the R. capsulatus genome and were found to be clustered in similar operons consisting of the genes acxA (beta subunit), acxB (alpha subunit), and acxC (gamma subunit). Transposon mutagenesis of X. autotrophicus revealed a requirement of sigma(54) and a sigma(54)-dependent transcriptional activator (AcxR) for acetone-dependent growth and acetone carboxylase gene expression. A potential sigma(54)-dependent promoter 122 bp upstream of X. autotrophicus acxABC was identified. An AcxR gene homolog was identified 127 bp upstream of acxA in R. capsulatus, but this activator lacked key features of sigma(54)-dependent activators, and the associated acxABC lacked an apparent sigma(54)-dependent promoter, suggesting that sigma(54) is not required for expression of acxABC in R. capsulatus. These studies reveal a conserved strategy of ATP-dependent acetone carboxylation and the involvement of transcriptional enhancers in acetone carboxylase gene expression in gram-negative acetone-utilizing bacteria.
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PMID:Biochemical, molecular, and genetic analyses of the acetone carboxylases from Xanthobacter autotrophicus strain Py2 and Rhodobacter capsulatus strain B10. 1200 37

The maltose system of Escherichia coli consists of a number of genes encoding proteins involved in the uptake and metabolism of maltose and maltodextrins. The system is positively regulated by MalT, its transcriptional activator. MalT activity is controlled by two regulatory circuits: a positive one with maltotriose as effector and a negative one involving several proteins. MalK, the ATP-hydrolyzing subunit of the cognate ABC transporter, MalY, an enzyme with the activity of a cystathionase, and Aes, an acetyl esterase, phenotypically act as repressors of MalT activity. By in vivo titration assays, we have shown that the N-terminal 250 amino acids of MalT contain the interaction site for MalY but not for MalK. This was confirmed by gel filtration analysis, where MalY was shown to coelute with the N-terminal MalT structural domain. Mutants in MalT causing elevated mal gene expression in the absence of exogenous maltodextrins were tested in their response to the three repressors. The different MalT mutations exhibited a various degree of sensitivity towards these repressors, but none was resistant to all of them. Some of them became nearly completely resistant to Aes while still being sensitive to MalY. These mutations are located at positions 38, 220, 243, and 359, most likely defining the interaction patch with Aes on the three-dimensional structure of MalT.
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PMID:The N terminus of the Escherichia coli transcription activator MalT is the domain of interaction with MalY. 1200 49

The class II transactivator (CIITA) is the key regulator of major histocompatibility complex (MHC) class II gene transcription. We demonstrate here that CIITA requires the ATPase subunit of an hSWI/SNF complex, brahma-related gene 1 (BRG-1), to activate transcription. When introduced into a cell line lacking BRG-1, CIITA was unable to activate cellular MHC class II genes. Reexpression of the wild-type but not an ATP-binding-deficient BRG-1 protein in this cell line restored the ability of CIITA to transactivate transcription of MHC class II genes. Interestingly, when the activity of CIITA was assayed in the BRG-1-deficient cell line by using a plasmid-based reporter assay, BRG-1 was not required for transcriptional activation, suggesting that the chromatin structure on the plasmid is such that BRG-1 is not necessary. Coimmunoprecipitation experiments were performed to determine if BRG-1 and CIITA proteins associate with each other in cells. We found that the two proteins coimmunoprecipitate and that amino acids 1 to 140 of CIITA are sufficient for binding. Taken together, these data suggest that BRG-1 and, very likely, an hSWI/SNF complex are required for transcription of MHC class II genes. The complex is likely recruited to MHC class II promoters, at least in part, by interaction with CIITA.
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PMID:The class II transactivator requires brahma-related gene 1 to activate transcription of major histocompatibility complex class II genes. 1207 31

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