Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many proteins of the SNF2 family, which share a similar DNA-dependent ATPase/putative helicase domain, are involved in global transcriptional control and processing of DNA damage. We report here the partial cloning and characterization of 89B helicase, a gene encoding a new Drosophila melanogaster member of the SNF2 family. 89B Helicase protein shows a high degree of homology in its ATPase/helicase domain to the global transcriptional activators SNF2 and Brahma and to the DNA repair proteins ERCC6 and RAD54. It is, however, most strikingly similar to the Saccharomyces cerevisiae protein Mot1, a transcriptional repressor with many target genes for which no homologue has yet been described. 89B helicase is expressed throughout fly development and its large transcript encodes a >200 kDa protein. Staining with anti-89B Helicase antibodies reveals that the protein is present uniformly in early embryos and then becomes localized to the ventral nerve cord and brain. On the polytene chromosomes, 89B Helicase is bound to several hundred specific sites that are randomly distributed. The homology of 89B Helicase to Mot1, its widespread developmental expression and its large number of targets on the polytene chromosomes of larval salivary gland cells suggest that 89B Helicase may play a role in chromosomal metabolism, particularly global transcriptional regulation.
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PMID:Expanding the Mot1 subfamily: 89B helicase encodes a new Drosophila melanogaster SNF2-related protein which binds to multiple sites on polytene chromosomes. 877 90

Cells require optimum protein synthetic activity in order to support cell proliferation, maintain homeostatic and metabolic integrity, and repair damage. Since growth depends on protein synthesis through ribosome biogenesis, the control of biosynthesis of ribosomes is necessarily a key element for control of growth. Nucleolin is a major nucleolar protein of exponentially growing eukaryotic cells, which is directly involved in the regulation of ribosome biogenesis and maturation. The highly conserved nucleolin contains three major domains through which it controls the organization of nucleolar chromatin, packaging of pre-RNA, rDNA transcription, and ribosome assembly. Numerous reports have implicated the involvement of nucleolin either directly or indirectly in the regulation of cell proliferation and growth, cytokinesis, replication, embryogenesis, and nucleogenesis. Nucleolin, an RNA binding protein, is also an autoantigen, a transcriptional repressor, and a switch region targeting factor. In addition, nucleolin exhibits autodegradation, DNA and RNA helicase activities, and DNA-dependent ATPase activity. An interesting aspect of nucleolin action is that it is a target for regulation by proteolysis, methylation, ADP-ribosylation, and phosphorylation by CKII, cdc2, PKC-xi, cyclic AMP-dependent protein kinase, and ecto-protein kinase. For these and other reasons, nucleolin is fundamental to the survival and proliferation of cells. Considerable progress has been made in recent years with the identification of new nucleolin binding proteins that may mediate these many nucleolin-dependent functions. Nucleolin also functions as a cell surface receptor, where it acts as a shuttling protein between cytoplasm and nucleus, and thus can even provide a mechanism for extracellular regulation of nuclear events. Exploration of the regulation of this multifaceted protein in a remarkable number of diverse functions is challenging.
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PMID:Molecular dissection of nucleolin's role in growth and cell proliferation: new insights. 1054 74

dMi-2, the ATPase subunit of the Drosophila nucleosome remodelling and histone deacetylation (dNuRD) complex, was identified in a two-hybrid screen as an interacting partner of the transcriptional repressor, Tramtrack69 (Ttk69). A short region of Ttk69 is sufficient to mediate this interaction. Ttk69, but not the Ttk88 isoform, co-purifies with the dNuRD complex isolated from embryo extracts. dMi-2 and Ttk69 co-immunoprecipitate from embryonic extracts, indicating that they can associate in vivo. Both dMi-2 and Ttk69 co-localize at a number of discrete sites on polytene chromosomes, showing that they bind common target loci. We also demonstrate that dMi-2 and Ttk interact genetically, indicating a functional interaction in vivo. We propose that Ttk69 represses some target genes by remodelling chromatin structure through the recruitment of the dNuRD complex.
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PMID:Tramtrack69 interacts with the dMi-2 subunit of the Drosophila NuRD chromatin remodelling complex. 1174 21

We report a cadmium- and lead-detecting transcriptional repressor from Mycobacterium tuberculosis designated CmtR. Two genes were co-transcribed with cmtR, one encoding a deduced P1 type ATPase. Purified CmtR bound to the cmt operator-promoter, and repression of transcription was lost after introduction of a stop codon into cmtR. Assays of metal-dependent expression from cmt and nmt operator-promoters established that the metal specificity of CmtR in vivo was perfectly inverted relative to the nickel-cobalt sensor NmtR from the same organism, with CmtR totally insensitive to Co(II) or Ni(II) and NmtR totally insensitive to Cd(II) or Pb(II). Absorption spectroscopy of Cd(II)-, Co(II)-, and Ni(II)-substituted CmtR revealed S- to metal-charge-transfer which was absent in NmtR, providing diagnostic metal-difference spectra that discriminated between metal-binding to these two proteins. Ni(II)-binding isothermal titrations of CmtR are complex, with Kapp = 1.8 x 10(4) m(-1) for site1, three orders of magnitude weaker than KNi for NmtR. Mixing equimolar apo-NmtR and apo-CmtR with 0.9 equivalents of Cd(II) gave Cd(II)-dependent difference spectra almost identical to Cd(II)0.9-CmtR. Thus, Cd(II) bound to CmtR in preference to NmtR, whereas the converse was true for Ni(II); this correlates faithfully with and provides a simplistic basis for metal-sensing preferences. In contrast, CmtR and NmtR had similar affinities for Co(II), and alternative explanations for Co(II) sensitivities are invoked. ArsR-SmtB repressors detect metals through derivatives of one or both of two possible allosteric sites at either carboxyl-terminal alpha5 helices or helix alpha3 proximal to the DNA-binding site. Unexpectedly, neither site was required for inducer recognition by CmtR. The mutants in potential metal ligands in, or near, these regions, Cys4, Cys35, Asp79, His81, Asp97, Asp99, Glu105, Glu111, and Glu114, retained both repression and inducer recognition. Crucially, substitution of Cys57, Cys61, and Cys102 with Ser revealed that each of these three residues is obligatory for Cd(II) detection, and this defines completely new sensory sites.
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PMID:A cadmium-lead-sensing ArsR-SmtB repressor with novel sensory sites. Complementary metal discrimination by NmtR AND CmtR in a common cytosol. 1293 64

The ATP-dependent protease Clp plays important roles in the cell's protein quality control system and in the regulation of cellular processes. In Corynebacterium glutamicum, the levels of the proteolytic subunits ClpP1 and ClpP2 as well as of the corresponding mRNAs were drastically increased upon deletion of the clpC gene, coding for a Clp ATPase subunit. We identified a regulatory protein, designated ClgR, binding to a common palindromic sequence motif in front of clpP1P2 as well as of clpC. Deletion of clgR in the DeltaclpC background completely abolished the increased transcription of both operons, indicating that ClgR activates transcription of these genes. ClgR activity itself is probably controlled via ClpC-dependent regulation of its stability, as ClgR is only present in DeltaclpC and not in wild-type cells, whereas the levels of clgR mRNA are comparable in both strains. clpC, clpP1P2 and clgR expression is induced upon severe heat stress, however, independently of ClgR. Identification of the heat-responsive transcriptional start sites in front of these genes revealed the presence of sequence motifs typical for sigmaECF-dependent promoters. The ECF sigma factor sigmaH could be identified as being required for transcriptional activation of clpC, clpP1P2 and clgR in response to severe heat stress. A second heat-responsive but sigmaH-independent promoter in front of clgR could be identified that is subject to negative regulation by the transcriptional repressor HspR. Taken together, these results show that clpC and clpP1P2 expression in C. glutamicum is subject to complex regulation via both independent and hierarchically organized pathways, allowing for the integration of multiple environmental stimuli. Both the ClgR- and sigmaH-dependent regulation of clpC and clpP1P2 expression appears to be conserved in other actinomycetes.
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PMID:clpC and clpP1P2 gene expression in Corynebacterium glutamicum is controlled by a regulatory network involving the transcriptional regulators ClgR and HspR as well as the ECF sigma factor sigmaH. 1504 27

MOT1 encodes an essential ATPase that functions as a general transcriptional regulator in vivo by modulating TATA-binding protein (TBP) DNA-binding activity. Although MOT1 was originally identified both biochemically and in several genetic screens as a transcriptional repressor, a combination of subsequent genetic, chromatin immunoprecipitation, and microarray analysis suggested that MOT1 might also have an additional role in vivo as a transcriptional activator. To better understand the role(s) of MOT1 in vivo, we selected for genomic suppressors of a mot1 temperature-sensitive mutation. This selection identified mutations in SPT15 (TBP) and BUR6, both of which are clearly linked with MOT1 at the functional level. The vast majority of the suppressor mutations, however, unexpectedly occurred in six genes that encode known components of the SUMO pathway and in two other genes with unknown functions, SLX5 and SLX8. Additional results presented here, including extensive synthetic lethality observed between slx5delta and slx8delta and SUMO pathway mutations, suggest that SLX5 and SLX8 are new components or regulators of the SUMO pathway and that SUMO modification might have a general role in transcriptional regulation as part of the TBP regulatory network.
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PMID:Genetic analysis connects SLX5 and SLX8 to the SUMO pathway in Saccharomyces cerevisiae. 1638 68

The ATP-dependent chromatin remodeller Mi-2 functions as a transcriptional repressor and contributes to the suppression of cell fates during development in several model organisms. Mi-2 is the ATPase subunit of the conserved Nucleosome Remodeling and Deacetylation (NuRD) complex, and transcriptional repression by Mi-2 is thought to be dependent on its associated histone deacetylase. Here, we have purified a novel dMi-2 complex from Drosophila that is distinct from dNuRD. dMec (dMEP-1 complex) is composed of dMi-2 and dMEP-1. dMec is a nucleosome-stimulated ATPase that is expressed in embryos, larval tissues and adult flies. Surprisingly, dMec is far more abundant than dNuRD and constitutes the major dMi-2-containing complex. Both dNuRD and dMec associate with proneural genes of the achaete-scute complex. However, despite lacking a histone deacetylase subunit, only dMec contributes to the repression of proneural genes. These results reveal an unexpected complexity in the composition and function of Mi-2 complexes.
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PMID:dMec: a novel Mi-2 chromatin remodelling complex involved in transcriptional repression. 1916 47

Bacillus subtilis CsoR (Bsu CsoR) is a copper-sensing transcriptional repressor that regulates the expression of the copZA operon encoding a copper chaperone and a Cu efflux P-type ATPase, respectively. Bsu CsoR is a homologue of Mycobacterium tuberculosis CsoR (Mtb CsoR), representative of a large Cu(I)-sensing regulatory protein family. We show here that Bsu CsoR binds approximately 1 mol equiv of Cu(I) per monomer in vitro with an affinity >or=10(21) M(-1). X-ray absorption spectroscopy shows Cu(I) adopts a trigonal S(2)N coordination like Mtb CsoR. Both apo and Cu(I)-bound Bsu CsoR are stable tetramers in the low micromolar monomer concentration range by sedimentation velocity and equilibrium ultracentrifugation. Apo-Bsu CsoR binds to a pseudopalindromic 30 bp copZA operator-promoter DNA with a stoichiometry of two tetramers per DNA and stepwise affinities of K(1)(apo) = 3.1(+/-0.8) x 10(7) M(-1) and K(2)(apo) = 8.3 (+/-2.2) x 10(7) M(-1) (0.4 M NaCl, 25 degrees C, pH 6.5). Cu(I) Bsu CsoR binds to the same DNA with greatly reduced affinities, K(1)(Cu) = 2.9(+/-0.4) x 10(6) M(-1) and K(2)(Cu) <or= 1.0 x 10(5) M(-1) consistent with a copper-dependent derepression model. This Cu-dependent regulation is abrogated by a "second shell" Glu90-to-Ala substitution. Bsu CsoR binds Ni(II) with very high affinity but forms a non-native coordination geometry, as does Co(II) and likely Zn(II); none of these metals strongly regulates copZA operator DNA binding in vitro. The implications of these findings on the specificity of metal-sensing sites in CsoR/RcnR proteins are discussed.
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PMID:Molecular insights into the metal selectivity of the copper(I)-sensing repressor CsoR from Bacillus subtilis. 1924 60

Switches between different phenotypes and their underlying states of gene transcription occur as cells respond to intrinsic developmental cues or adapt to changing environmental conditions. Post-translational modification of the master regulatory transcription factors that define the initial phenotype is a common strategy to direct such transitions. Emerging evidence indicates that the modification of key transcription factors by the small polypeptide ubiquitin has a central role in many of these transitions. However, the molecular mechanisms by which ubiquitylation regulates the switching of promoters between active and inactive states are largely unknown. Ubiquitylation of the yeast transcriptional repressor alpha2 is necessary to evoke the transition between mating-types, and here we dissect the impact of this modification on alpha2 dynamics at its target promoters. Ubiquitylation of alpha2 does not alter DNA occupancy by depleting the existing pool of the transcription factor, despite its well-characterized function in directing repressor turnover. Rather, alpha2 ubiquitylation has a direct role in the rapid removal of the repressor from its DNA targets. This disassembly of alpha2 from DNA depends on the ubiquitin-selective AAA-ATPase Cdc48. Our findings expand the functional targets of Cdc48 to include active transcriptional regulatory complexes in the nucleus. These data reveal an ubiquitin-dependent extraction pathway for dismantling transcription factor-DNA complexes and provide an archetype for the regulation of transcriptional switching events by ubiquitylation.
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PMID:A ubiquitin-selective AAA-ATPase mediates transcriptional switching by remodelling a repressor-promoter DNA complex. 1991 56

The TTHA1719 gene from Thermus thermophilus HB8 encodes an orthologue of the copper-sensing transcriptional repressor CsoR. X-ray crystal structure analysis of T. thermophilus CsoR indicated that it forms a homotetramer. The structures of the CsoR monomer and dimer are similar to those of Mycobacterium tuberculosis CsoR. In the absence of copper ions, T. thermophilus CsoR bound to the promoter region of the copper-sensitive operon copZ-csoR-copA, which encodes the copper chaperone CopZ, CsoR and the copper efflux P-type ATPase CopA, to repress their expression, while in the presence of approximately an equal amount of copper ion, CsoR was released from the DNA, to allow expression of the downstream genes. Both Cu(II) and Cu(I) ions could bind CsoR, and were effective for transcriptional derepression. Additionally, CsoR could also sense various other metal ions, such as Zn(II), Ag(I), Cd(II) and Ni(II), which led to transcriptional derepression. The copper-binding motif of T. thermophilus CsoR contains C-H-H, while those of most orthologues contain C-H-C. The X-ray crystal structure of T. thermophilus CsoR suggests that a histidine residue in the N-terminal domain is also involved in metal-ion binding; that is, the binding motif could be H-C-H-H, like that of Escherichia coli RcnR, which binds Ni(II)/Co(II). The non-conserved H70 residue in the metal-binding motif of T. thermophilus CsoR is important for its DNA-binding affinity and metal-ion responsiveness.
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PMID:Structural and functional characterization of the transcriptional repressor CsoR from Thermus thermophilus HB8. 2039 70


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