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 generation of an accessible heat shock promoter in chromatin in vitro requires the concerted action of the GAGA transcription factor and NURF, an ATP-dependent nucleosome remodeling factor. NURF is composed of four subunits and is biochemically distinct from the SWI2/SNF2 multiprotein complex, a transcriptional activator that also appears to alter nucleosome structure. We have obtained protein microsequence and immunological evidence identifying the 140 kDa subunit of NURF as ISWI, previously of unknown function but highly related to SWI2/SNF2 only in the ATPase domain. The ISWI protein is localized to the cell nucleus and is expressed throughout Drosophila development at levels as high as 100,000 molecules/cell. The convergence of biochemical and genetic studies on ISWI and SWI2/SNF2 underscores these ATPases and their close relatives as key components of independent systems for chromatin remodeling.
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PMID:ISWI, a member of the SWI2/SNF2 ATPase family, encodes the 140 kDa subunit of the nucleosome remodeling factor. 852 2

The final sigma54-dependent DmpR activator regulates transcription of the dmp operon that encodes the enzymes for catabolism of (methyl)phenols. DmpR is expressed constitutively, but its transcriptional promoting activity is controlled positively in direct response to the presence of aromatic pathway substrates (effectors). DmpR has a distinct domain structure with the amino-terminal A-domain controlling the specificity of activation of the regulator by aromatic effectors (signal reception), a central C-domain mediating an ATPase activity essential for transcriptional activation, and a carboxyl-terminal D-domain involved in DNA binding. Deletion of the A-domain has been shown previously to result in an effector-independent transcriptional activator with constitutive ATPase activity. These results, in conjunction with the location of mutations within the A- and C-domains which exhibit an effector-independent (semiconstitutive) property, have led to a working model in which the A-domain serves to mask the ATPase and transcriptional promoting activity of the C-domain in the absence of effectors. To investigate the mechanism by which the A-domain exerts its repressive effect, we developed a genetic system to select positively for intramolecular second site revertants of DmpR. The results demonstrate (i) that mutations within the A-domain can suppress the semiconstitutive activity of C-domain located mutations and vice versa; (ii) that the C-domain located mutations do not influence the intrinsic ATPase and transcriptional promoting property of the C-domain in the absence of the A-domain; and (iii) that semiconstitutive mutations of the A- and C-domain have an additive effect. Taken together these results support a model in which the A-domain represses the function(s) of the C-domain by direct interactions between residues of the two domains.
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PMID:Genetic evidence for interdomain regulation of the phenol-responsive final sigma54-dependent activator DmpR. 866 26

Using a genetic strategy designed to find proteins involved in the function of the Saccharomyces cerevisiae transcriptional activator GAL4, we isolated mutants in two genes which rescue a class of gal4 activation domain mutants. One of these genes, SUG1, encodes a member of a large family of putative ATPases, the Conserved ATPase containing Domain (CAD) proteins (also known as AAA proteins) that are involved in a wide variety of cellular functions. Subsequently, SUG1 was identified as a subunit of the 26 S proteasome. We have now cloned the gene defined by the second complementation group. SUG2 encodes an essential 49-kDa protein that is also a member of the CAD family and is 43% identical to SUG1. The mutation in sug2-1, like that in sug1-1, is found in the CAD near the highly conserved ATPase motif. We present biochemical and genetic evidence that SUG2 is associated in vivo with SUG1 and is a novel CAD protein subunit of the 26 S proteasome. With its highly conserved mammalian homologs, human p42 and ground squirrel CADp44, SUG2 defines a new class of proteasomal CAD proteins.
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PMID:Isolation and characterization of SUG2. A novel ATPase family component of the yeast 26 S proteasome. 895 18

By using transposon insertional mutagenesis and deletion analyses, a recombinant clone containing the region upstream of the acoABCD operon of Klebsiella pneumoniae was found to be required for acetoin-inducible expression of the operon in Escherichia coli. The nucleotide sequence of the region was determined, and it displayed an open reading frame of 2,763 bp that is transcribed divergently to the acoABCD operon. This gene, designated acoK, is capable of encoding a protein with an overall 58.4% amino acid identity with MalT, the transcriptional activator of the E. coli maltose regulon. A conserved sequence for nucleotide binding at the N-terminal region, as well as a helix-turn-helix motif belonging to the LuxR family of transcriptional regulators at the C terminus, was also identified. Primer extension analysis identified two transcription initiation sites, S1 and S2, located 319 and 267 bp, respectively, upstream of the putative start codon of acoK. Several copies of NtrC recognition sequence [CAC-(N11 to N18)-GTG] were found in the promoter regions of both the acoK gene and the acoABCD operon. Acetoin-dependent expression of the acoABCD operon could be restored in the E. coli acoK mutants by supplying a plasmid carrying an intact acoK, suggesting a transactivating function of the gene product. The AcoK protein overproduced in E. coli was approximately 100 kDa, which is in good agreement with the molecular mass deduced from the nucleotide sequence. A specific DNA binding property and an ATPase activity of the purified AcoK were also demonstrated.
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PMID:Identification and characterization of acoK, a regulatory gene of the Klebsiella pneumoniae acoABCD operon. 904 5

The hepatocyte nuclear factor-3 (HNF-3)/fork head homolog (HFH) proteins are an extensive family of transcription factors, which share homology in the winged helix DNA binding domain. Members of the HFH/winged helix family have been implicated in cell fate determination during pattern formation, in organogenesis, and in cell-type-specific gene expression. In this study we isolated a full-length HFH-3 cDNA clone from a human kidney library which encoded a 351-amino acid protein containing a centrally located winged helix DNA binding domain. We demonstrate that HFH-3 is a potent transcriptional activator requiring 138 C-terminal residues for activity. We used in situ hybridization to demonstrate that HFH-3 expression is restricted to the epithelium of the renal distal convoluted tubules. We determined the HFH-3 DNA binding consensus sequence by in vitro DNA binding site selection using recombinant HFH-3 protein and used this consensus sequence to identify putative HFH-3 target genes expressed there. These putative HFH-3 target genes include the Na/K-ATPase, Na/H and anion exchangers, E-cadherin, and mineralocorticoid receptor genes as well as genes for the transcription factors HNF-1, vHNF-1, and HNF-4.
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PMID:The winged helix transcriptional activator HFH-3 is expressed in the distal tubules of embryonic and adult mouse kidney. 915 25

Rhizobium meliloti DctD (C4-dicarboxylate transport protein D) is a transcriptional activator that catalyzes the ATP-dependent isomerization of closed complexes between sigma 54-RNA polymerase holoenzyme and the dctA promoter to open complexes. Following random mutagenesis of dctD, 55 independent mutant forms of DctD that failed to activate transcription from a dctA'-'lacZ reporter gene in Escherichia coli were selected, and the amino acid substitutions were determined for these mutant proteins. Amino acid substitutions were distributed throughout the central domain of the protein, the domain responsible for transcription activation, but most of the substitutions occurred within three highly conserved regions of the protein. Selected mutant proteins were purified, and their activities were studied in vitro. All of the purified mutant proteins appeared to have normal DNA-binding activity and interacted with sigma 54 and core RNA polymerase, as determined from protein crosslinking assays. Proteins with amino acid substitutions in a region spanning amino acid positions 222 to 225 retained their ATPase activities, whereas proteins with substitutions in other regions had little or no ATPase activity. Taken together, these data suggest that the region that encompasses amino acid residues 222 through 225 probably functions in coupling the energy released from ATP hydrolysis to open complex formation rather than as a major determinant for binding to RNA polymerase.
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PMID:Alterations within the activation domain of the sigma 54-dependent activator DctD that prevent transcriptional activation. 929 39

The mutation S170A in the proposed nucleotide binding site of the transcriptional activator protein NTRC abolishes its ability to catalyse open promoter complex formation by the sigma(N)-RNA polymerase holoenzyme. NTRC(S170A) has significant ATPase activity, which, in contrast to the wild-type protein, is unaffected by phosphorylation or binding to enhancer sites on DNA. The mutant protein appears to oligomerise normally on DNA in response to phosphorylation but the ATPase activity is apparently not responsive to changes in oligomerisation state. The defect in transcriptional activation is discussed in relation to mutations in other sigma(N)-dependent activators.
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PMID:Properties of a mutant form of the prokaryotic enhancer binding protein, NTRC, which hydrolyses ATP in the absence of effectors. 980 74

The nmd mouse mutation causes progressive degeneration of spinal motor neurons and muscle atrophy. We identified the mutated gene as the putative transcriptional activator and ATPase/DNA helicase previously described as Smbp2, Rip1, Gf1, or Catf1. Mutations were found in two alleles-a single amino acid deletion in nmdJ and a splice donor mutation in nmd2J. The selective vulnerability of motor neurons is striking in view of the widespread expression of this gene, although the pattern of degeneration may reflect a specific threshold since neither allele is null. In addition, the severity of the nmd phenotype is attenuated in a semidominant fashion by a major genetic locus on chromosome (Chr) 13. The identification of the nmd gene and mapping of a major suppressor provide new opportunities for understanding mechanisms of motor neuron degeneration.
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PMID:Identification of the mouse neuromuscular degeneration gene and mapping of a second site suppressor allele. 988 26

The ftsH gene encodes an ATP- and Zn(2+)-dependent metalloprotease with a molecular mass of about 70 kDa. It was first identified in Escherichia coli where it is also designated hflB, tolZ or mrsC, and seems to be present in most if not all bacteria. The FtsH protein is anchored to the cytoplasmic membrane via two transmembrane regions in such a way that the very short amino- and the long carboxy-termini are exposed into the cytoplasm. FtsH is member of the AAA family (ATPases associated with a variety of cellular activities) which are characterized by a module of about 200 amino acid residues in length containing an ATP-binding site. In Escherichia coli, FtsH forms a complex with a pair of periplasmically exposed membrane proteins, HflK and HflC. The E. coli enzyme is required for proteolytic degradation of some unstable proteins that include both soluble regulatory proteins such as sigma 32 (heat-shock sigma factor) and phage lambda CII (transcriptional activator), and membrane proteins including uncomplexed forms of SecY (forms the translocon together with SecE and SecG) and the a subunit of the F0 complex of the H(+)-ATPase. Its activity can be modulated by the HflKC proteins, by another membrane protein designated YccA which can transiently associate with both the FtsH and the HflKC proteins, or by small peptides such as CIII encoded by phage lambda (involved in lysogenization) or SpoVM (needed for sporulation) encoded by Bacillus subtilis. Besides being a protease, there is circumstantial evidence that FtsH also acts as a molecular chaperone. It influences protein assembly in and through the cytoplasmic membrane and associates with denatured alkaline phosphatase without degrading it. Therefore, FtsH may serve to maintain quality control of some cytoplasmic and membrane proteins. Such ATP-dependent proteases with intrinsic chaperone activity have been designated charonins.
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PMID:FtsH--a single-chain charonin? 1007 51

We have constructed transgenic Drosophila melanogaster lines that express green fluorescent protein (GFP) exclusively in the nervous system. Expression is controlled with transcriptional regulatory elements present in the 5' flanking DNA of the Drosophila Na(+), K(+)-ATPase beta-subunit gene Nervana2 (Nrv2). This regulatory DNA is fused to the yeast transcriptional activator GAL4, which binds specifically to a sequence motif termed the UAS (upstream activating sequence). Drosophila lines carrying Nrv2-GAL4 transgenes have been genetically recombined with UAS-GFP (S65T) transgenes (Nrv2-GAL4+UAS-GFP) inserted on the same chromosomes. We observe strong nervous system-specific fluorescence in embryos, larvae, pupae, and adults. The GFP fluorescence is sufficiently bright to allow dynamic imaging of the nervous system at all of these developmental stages directly through the cuticle of live Drosophila. These lines provide an unprecedented view of the nervous system in living animals and will be valuable tools for investigating a number of developmental, physiological, and genetic neurobiological problems.
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PMID:Dynamic visualization of nervous system in live Drosophila. 1046 27


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