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 common plant regulatory factors (CPRFs) from parsley are transcription factors with a basic-leucine-zipper motif that bind to cis-regulatory elements frequently found in promoters of light-regulated genes. Proposed to function in concert with members of other transcription factor families, CPRFs regulate the transcriptional activity of many target genes. Here, we report that, in contrast to CPRF2, which operates as a transcriptional activator, CPRF1 functions as repressor in vivo. Two-hybrid screens using CPRF1 and CPRF2 as "baits" resulted in the isolation of four novel parsley proteins which interact with either CPRF1 or CPRF2 in vivo. Three of these factors represent new parsley bZIP factors, designated CPRF5-CPRF7, whereas the fourth, named CPRF1-interacting protein (CIP), shows no homology to any other known protein. CPRF5 and CIP specifically interact with CPRF1, whilst CPRF6 and CPRF7 exclusively form heterodimers with CPRF2. CPRF5, CPRF6 and CPRF7 are transcription factors that exhibit sequence-specific DNA-binding as well as transactivation abilities, whereas the function of CIP remains elusive. The newly isolated CPRFs and CIP are constitutively localized in the nucleus in parsley protoplasts. Furthermore, mRNA accumulation studies revealed that the expression of these novel bZIP genes and CIP is not altered by exposure to light. We discuss the possible roles of the newly identified proteins in CPRF1- and CPRF2-dependent target gene expression.
 ...
PMID:Isolation and characterization of four novel parsley proteins that interact with the transcriptional regulators CPRF1 and CPRF2. 1152 88

Lrp is a global regulator of metabolism in Escherichia coli that helps cells respond to changes in environmental conditions. The action of Lrp as a transcriptional activator or repressor is sometimes affected by whether the medium contains exogenous leucine. The abundance of Lrp in cells is relatively high (about 15 microM in monomer), and given the relatively high Lrp binding affinity in vitro for specific binding sites (nanomolar apparent dissociation constants), the expectation is that all binding sites will be saturated with Lrp in vivo. Here we consider the fraction of the total Lrp in cells that is free and the fraction that is bound to DNA. Using minicell-producing strains, we measured the distribution of Lrp between cytoplasm and nucleoid in cells grown under different nutritional conditions and in cells in different phases of growth. In E. coli cells grown in minimal medium to mid-log phase, the ratio of free to DNA-bound Lrp was about 0.67. This ratio decreased about threefold when the cells were grown in minimal medium supplemented with leucine. Our results also confirmed the previous finding that growth rate regulates lrp expression by as much as three to fourfold. Growth rate-regulated lrp expression, along with changes in the extent of non-specific binding, influences the level of free Lrp in vivo over a 16-fold range. We propose that the net effect of these processes is to regulate the relative concentrations of free Lrp hexadecamer and leucine-bound octamer, leading to promoter selection in response to environmental conditions.
 ...
PMID:Modulation of Lrp action in Escherichia coli by leucine: effects on non-specific binding of Lrp to DNA. 1174 23

Transcription of lysine genes in Saccharomyces cerevisiae is dependent on Lys14p and on alpha-aminoadipate semialdehyde (alphaAASA), an intermediate of the pathway. The two-thirds C-terminal end of Lys14p is sufficient to ensure the activation function of the protein and its modulation by alphaAASA. Here, we show that no single discrete domain of Lys14p is able to activate transcription and that most of the deleted LexA-Lys14p proteins are inactive even in the presence of a high alphaAASA concentration. The point mutations abolishing the activation capacity of Lys14p are distributed all over the entire C-terminal segment. Although the deletion of 20 residues rich in leucine and located downstream of the DNA-binding domain converts Lys14p to a constitutive transcriptional activator, our analysis provides evidence that the modulation process of Lys14p activity does not involve an effector-dependent masking/unmasking mechanism. Furthermore, we show that the protein chaperone Hsp82p is required for full activation of LYS genes by the alphaAASA-activated Lys14p as well as by the constitutive Lys14p. Our results suggest that the proper folding of the two-thirds C-terminal portion of Lys14p is essential not only to activate transcription but also to modulate it according to alphaAASA concentration.
 ...
PMID:The proper folding of a long C-terminal segment of the yeast Lys14p regulator is required for activation of LYS genes in response to the metabolic effector. 1195 10

Lrp is a global regulator of metabolism in Escherichia coli that helps cells respond to changes in environmental conditions. The action of Lrp as a transcriptional activator or repressor is sometimes affected when the medium contains exogenous leucine. In this study, we examined the thermodynamics of leucine binding to Lrp and to a leucine response mutant, Lrp-1, and leucine-induced dissociation of Lrp hexadecamer to leucine-bound octamer. The results of dynamic light-scattering and fluorescence measurements suggest that Lrp has two leucine-binding sites, one a high-affinity site and the other a low-affinity site that is coupled to the dissociation reaction. The Gibbs free energy change for leucine binding to the high-affinity site is about -7.0 kcal/mol. Binding of two leucine molecules to low-affinity sites on the hexadecamer or one leucine molecule to one octamer induces the dissociation of hexadecamer to leucine-bound octamer. The Gibbs free energy change for leucine binding to the low-affinity site was estimated to be in the range -4.66 to -5.03 kcal/mol for leucine binding to an octamer or -6.01 to -6.75 kcal/mol for leucine binding to a hexadecamer. The thermodynamic parameters derived from this study were used together with other data to estimate the distribution of free Lrp hexadecamer, octamer, leucine-bound hexadecamer, and leucine-bound octamer in cells. Mathematical modeling, employed to simulate modulation of Lrp action in response to growth conditions, gave results that are consistent with known patterns of Lrp action on different operons.
 ...
PMID:Leucine-induced dissociation of Escherichia coli Lrp hexadecamers to octamers. 1205

Host-encoded functions that regulate the transfer operon (tra) in the virulence plasmid of Salmonella enterica (pSLT) were identified with a genetic screen. Mutations that decreased tra operon expression mapped in the lrp gene, which encodes the leucine-responsive regulatory protein (Lrp). Reduced tra operon expression in an Lrp- background is caused by lowered transcription of the traJ gene, which encodes a transcriptional activator of the tra operon. Gel retardation assays indicated that Lrp binds a DNA region upstream of the traJ promoter. Deletion of the Lrp binding site resulted in lowered and Lrp-independent traJ transcription. Conjugal transfer of pSLT decreased 50-fold in a Lrp- background. When a FinO- derivative of pSLT was used, conjugal transfer from an Lrp- donor decreased 1000-fold. Mutations that derepressed tra operon expression mapped in dam, the gene encoding Dam methyltransferase. Expression of the tra operon and conjugal transfer remain repressed in an Lrp- Dam- background. These observations support the model that Lrp acts as a conjugation activator by promoting traJ transcription, whereas Dam methylation acts as a conjugation repressor by activating FinP RNA synthesis. This dual control of conjugal transfer may also operate in other F-like plasmids such as F and R100.
 ...
PMID:Conjugal transfer of the virulence plasmid of Salmonella enterica is regulated by the leucine-responsive regulatory protein and DNA adenine methylation. 1206 46

The role of leucine biosynthesis by Sinorhizobium meliloti in the establishment of nitrogen-fixing symbiosis with alfalfa ( Medicago sativa) was investigated. The leuA gene from S. meliloti, encoding alpha-isopropylmalate synthase, which catalyses the first specific step in the leucine biosynthetic pathway, was characterized. S. melilotiLeuA(-) mutants were Leu auxotrophs and lacked alpha-isopropylmalate synthase activity. In addition, leuA auxotrophs were unable to nodulate alfalfa. Alfalfa roots did not seem to secrete enough leucine to support growth of leucine auxotrophs in the rhizosphere. Thus, this growth limitation probably imposes the inability to initiate symbiosis. However, in addition to the leucine auxotrophy, leuA strains were impaired in activation of nodulation genes by the transcriptional activator NodD1 in response to the plant flavone luteolin. By contrast, nod gene activation by NodD3, which does not involve plant-derived inducers, was unaffected. Our results suggest that a leucine-related metabolic intermediate may be involved in activation of nodulation genes by NodD1 and luteolin. This kind of control could be of relevance as a way to link bacterial physiological status to the response to plant signals and initiation of symbiosis.
 ...
PMID:Involvement of the Sinorhizobium meliloti leuA gene in activation of nodulation genes by NodD1 and luteolin. 1207 Jul 67

Activation of class II major histocompatibility complex (MHC) gene expression is regulated by a master regulator, class II transcriptional activator (CIITA). Transactivation by CIITA requires its nuclear import. This study will address a mechanistic role for the leucine-rich repeats (LRR) of CIITA in regulating nuclear translocation by mutating 12 individual consensus-motif "leucine" residues in both its alpha-motifs and beta-motifs. While some leucine mutations in the LRR motif of CIITA cause congruent loss of transactivation function and nuclear import, other alanine substitutions in both the alpha-helices and the beta-sheets have normal transactivation function but a loss of nuclear accumulation (i.e., functional mutants). This seeming paradox is resolved by the observations that nuclear accumulation of these functional mutants does occur but is significantly less than wild-type. This difference is revealed only in the presence of leptomycin B and actinomycin D, which permit examination of nuclear accumulation unencumbered by nuclear export and new CIITA synthesis. Further analysis of these mutants reveals that at limiting concentrations of CIITA, a dramatic difference in transactivation function between mutants and wild-type CIITA is easily detected, in agreement with their lowered nuclear accumulation. These experiments reveal an interesting aspect of LRR in controlling the amount of nuclear accumulation.
 ...
PMID:Leucine-rich repeats of the class II transactivator control its rate of nuclear accumulation. 1207 94

The cGvpE protein of Halobacterium salinarum PHH4 has been identified as transcriptional activator for the promoter of the c-gvpA gene encoding the major gas vesicle structural protein cGvpA. Molecular modelling of the carboxy-terminal region of cGvpE suggests that this protein resembles a basic leucine-zipper protein, and mutations in the putative DNA binding domain DNAB completely abolish the activator function in Haloferax volcanii transformants. Mutations in the key residues of the putative leucine-zipper region AH6 of cGvpE confirmed that the three residues V159, L166 and L173 were essential for the activator function of cGvpE at the c-gvpA promoter, whereas the cysteine residue C180 could be altered to a leucine or an aspartate residue without the loss of this function. Mutations in basic residues of helix AH4 demonstrated the importance of the lysine K104 for the activator function of cGvpE. A cGvpE protein containing a his-tag at the C-terminus was still able to activate the expression of c-gvpA in vivo. The cGvpE his-purified from Hf. volcanii formed a dimer in Blue-native polyacrylamide gels that could be resolved into monomers by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Dimers of cGvpE were already seen using SDS-PAGE, but not with cGvpE mutant proteins containing the alterations L166E or L173E/C180L in the leucine zipper. These results imply that the hydrophobic surface of helix AH6 is indeed required for the establishment of cGvpE dimers.
 ...
PMID:A bZIP protein from halophilic archaea: structural features and dimer formation of cGvpE from Halobacterium salinarum. 1212 60

CooA from Rhodospirillum rubrum is a heme-containing transcriptional activator that becomes activated only upon binding CO. The basis for this specificity has been probed in a CooA variant, termed DeltaP3R4 CooA, lacking two residues adjacent to the Pro(2) heme ligand, which weakens that ligand. DeltaP3R4 CooA can bind imidazole and CN(-), as well as CO, and form a 6-coordinate low spin adduct with each. However, in contrast to the case with CO, imidazole and CN(-) do not stimulate the DNA binding activity of DeltaP3R4 CooA. This result indicates that the CO-specific activation of CooA is not merely the result of creation of a 6-coordinate CooA adduct but that there must be another element to this response. One feature of CooA activation is modest repositioning of the C-helices upon CO binding, so we altered a portion of the C-helix (residues Ile(113) and Leu(116)) located near the heme-bound CO in wild type CooA, and we investigated the effect on CO-specific activation. Surprisingly, the sizes of Ile(113) and/or Leu(116) positions are not critical for CooA activation by CO, disproving a precise interaction between these residues and the CO-bound heme as a basis for the CO activation mechanism and CO ligand specificity. In contrast, hydrophobic residues at these positions contribute to the activation. Some CooA variants altered at these positions in the background of DeltaP3R4 were also found to show low but reproducible activation in response to imidazole binding to the heme. A model for the role of hydrophobicity in CooA activation and specificity is suggested.
 ...
PMID:The role of the hydrophobic distal heme pocket of CooA in ligand sensing and response. 1243 17

Trichomes of Arabidopsis are single-celled epidermal hair that are a useful model for studying plant cell fate determination. Trichome initiation requires the activity of the GLABROUS1 (GL1) gene whose expression in epidermal and trichome cells is dependent on the presence of a 3'-cis-regulatory element. Using a one-hybrid screen, we have isolated a cDNA, which encodes for a protein, GL1 enhancer binding protein (GeBP), that binds this regulatory element in yeast and in vitro. GeBP and its three homologues in Arabidopsis share two regions: a central region with no known motifs and a C-terminal region with a putative leucine-zipper motif. We show that both regions are necessary for trans-activation in yeast. A translational fusion with the Yellow Fluorescent Protein (YFP) indicates that GeBP is a nuclear protein whose localization is restricted to, on average, 3-5 subnuclear foci that might correspond to nucleoli. Transcriptional fusion with the GUS reporter indicates that GeBP is mainly expressed in vegetative meristematic tissues and in very young leaf primordia. We looked at GeBP expression in plants mutated in or misexpressing KNAT1, a KNOX gene, expressed in the shoot apical meristem and downregulated in leaf founder cells, and found that GeBP transcript level is regulated by KNAT1 suggesting that KNAT1 is a transcriptional activator of GeBP. This regulation suggests that GeBP is acting as a repressor of leaf cell fate.
 ...
PMID:GeBP, the first member of a new gene family in Arabidopsis, encodes a nuclear protein with DNA-binding activity and is regulated by KNAT1. 1253 44


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>