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)

Although normally absent, spontaneous pacemaker activity can develop in human atrium to promote tachyarrhythmias. HL-1 cells are immortalized atrial cardiomyocytes that contract spontaneously in culture, providing a model system of atrial cell automaticity. Using electrophysiologic recordings and selective pharmacologic blockers, we investigated the ionic basis of automaticity in atrial HL-1 cells. Both the sarcoplasmic reticulum Ca release channel inhibitor ryanodine and the sarcoplasmic reticulum Ca ATPase inhibitor thapsigargin slowed automaticity, supporting a role for intracellular Ca release in pacemaker activity. Additional experiments were performed to examine the effects of ionic currents activating in the voltage range of diastolic depolarization. Inhibition of the hyperpolarization-activated pacemaker current, If, by ivabradine significantly suppressed diastolic depolarization, with modest slowing of automaticity. Block of inward Na currents also reduced automaticity, whereas inhibition of T- and L-type Ca currents caused milder effects to slow beat rate. The major outward current in HL-1 cells is the rapidly activating delayed rectifier, IKr. Inhibition of IKr using dofetilide caused marked prolongation of action potential duration and thus spontaneous cycle length. These results demonstrate a mutual role for both intracellular Ca release and sarcolemmal ionic currents in controlling automaticity in atrial HL-1 cells. Given that similar internal and membrane-based mechanisms also play a role in sinoatrial nodal cell pacemaker activity, our findings provide evidence for generalized conservation of pacemaker mechanisms among different types of cardiomyocytes.
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PMID:Ionic mechanisms of pacemaker activity in spontaneously contracting atrial HL-1 cells. 2088 2

Human cancers utilise telomerase to maintain telomeres and prohibit cell senescence. Human telomerase reverse transcriptase (hTERT), an essential component of this complex, is regulated at the level of gene transcription. Using SILAC-proteomic analysis and molecular studies, we identified the AAA+ ATPase, RuvBl2 as a transcriptional regulator of hTERT and established that this regulation is through cooperation with Ets-2. In colon cancer patients, nuclear expression of RuvBl2 associated with nuclear expression of hTERT, pEts2 and advanced nodal disease (P<0.01, P=0.05 and P=0.03 respectively, n=170). These data firmly implicate RuvBl2 in Ets2 mediated regulation of hTERT in colon cancer which has functional and clinical consequences.
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PMID:RuvBl2 cooperates with Ets2 to transcriptionally regulate hTERT in colon cancer. 2176 15

We have developed a phylogeny-based design method that has been used to produce mutated proteins with enhanced thermal stabilities. We previously validated the predictive worth of the method by producing and characterizing mutants in which one original residue or a small number of the original residues had been replaced with the one or the ones found in the phylogenetically predicted "ancestral" sequence. For the current study, this method was used to design a sequence for the deepest nodal position of a phylogenic tree composed of 16 gyrase B-subunit sequences, which was then synthesized and characterized. The sequence was inferred from the sequences of 16 extant DNA gyrases and 3 extant type VI DNA topoisomerases. Genes encoding the inferred sequence and its N-terminal ATPase domain were PCR constructed and expressed in Escherichia coli. The full-length designed protein is slightly less thermally stable than is subunit B from the extant thermophilic Thermus thermophilus DNA gyrase, whereas the thermal stability of the designed ATPase domain is more similar to that of the T. thermophilus ATPase domain. Moreover, the designed ATPase domain has significant catalytic activity. Therefore, even a small set of homologous amino acid sequences contains sufficient information to design a thermally stable and functional protein. Because the isolated designed ATPase domain is more thermally stable and catalytically active than is the sequence containing the most frequently occurring amino acids among the 16 gyrases, the phylogenetic approach was superior (in this case, at least) to the consensus approach when the same data set was used to predict the two sequences.
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PMID:Phylogeny-based design of a B-subunit of DNA gyrase and its ATPase domain using a small set of homologous amino acid sequences. 2181 94

The control of ribosome biogenesis is a critical cellular nodal point, which ensures that protein synthesis is coordinated with cell growth and proliferation. Prior to their cytoplasmic assembly the 40S and 60S ribosomal subunits pass through the nucleolus and the nucleoplasm via a maturation pathway that involves a set of non-coding RNAs and non-ribosomal regulatory trans-acting factors. In mammalian cells the inventory of the required protein components is still fragmentary and it is largely unclear what drives the subcellular transitions and the exchange of protein components along the maturation pathway. However, recent data indicate that the dynamic post-translational modification by the ubiquitin-like SUMO modifier is critically involved in these processes. In particular, removal of SUMO from trans-acting factors by the SUMO-specific isopeptidase SENP3 is instrumental in the 60S maturation pathway in mammals. In an attempt to pinpoint the relevant targets of SENP3 we identified a novel SENP3-associated protein complex comprised of PELP1, TEX10 and WDR18. We demonstrated that this complex is involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the 60S ribosomal subunit. Importantly, we found that PELP1 is a SENP3-sensitive target of SUMO and observed that lack of SENP3-mediated desumoylation prevents the nucleolar partitioning of the PELP1-TEX10-WDR18 complex. SUMO-dependent subnuclear trafficking may thus assist in coordinating the rate of ribosome formation. Here we propose that sumoylation of PELP1 serves as a quality control mechanism that restricts pre-mature loading of the PELP1-WDR18-TEX10 complex to 60S particles thereby limiting ribosome maturation. We further hypothesize that the PELP1-associated AAA-ATPase MDN1 may be part of this surveillance pathway.
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PMID:SUMO routes ribosome maturation. 2206 70

The endoplasmic reticulum (ER) is a major intracellular calcium storage pool and a multifunctional organelle that accomplishes several calcium-dependent functions involved in many homeostatic and signaling mechanisms. Calcium is accumulated in the ER by Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA)-type calcium pumps. SERCA activity can determine ER calcium content available for intra-ER functions and for calcium release into the cytosol, and can shape the spatiotemporal characteristics of calcium signals. SERCA function therefore constitutes an important nodal point in the regulation of cellular calcium homeostasis and signaling, and can exert important effects on cell growth, differentiation and survival. In several cell types such as cells of hematopoietic origin, mammary, gastric and colonic epithelium, SERCA2 and SERCA3-type calcium pumps are simultaneously expressed, and SERCA3 expression levels undergo significant changes during cell differentiation, activation or immortalization. In addition, SERCA3 expression is decreased or lost in several tumor types when compared to the corresponding normal tissue. These observations indicate that ER calcium homeostasis is remodeled during cell differentiation, and may present defects due to decreased SERCA3 expression in tumors. Modulation of the state of differentiation of the ER reflected by SERCA3 expression constitutes an interesting new aspect of cell differentiation and tumor biology.
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PMID:Endoplasmic reticulum calcium pumps and cancer cell differentiation. 2497 Jan 32

Members of the protein superfamily of small guanosine triphosphatases, also known as small GTPases, small G-proteins, or the Ras superfamily, are involved in nearly every aspect of cell biology. Small GTPases are tightly regulated molecular switches that make binary on/off decisions through controlled loading of GTP (activation) and hydrolysis of GTP to GDP (inactivation). Small GTPases typically function as nodal points that integrate broad upstream regulatory inputs and disseminate broad effector outputs. The superfamily comprises five families that are conserved across eukaryotes: Ras, Rho, Rab, Arf, and Ran. Each family, besides Ran, has radiated functionally since our last common ancestor with fungi, and certain subfamilies persist throughout metazoa. The double genome duplication leading to vertebrates resulted in two to four genes for many subfamilies, plus some novel mammalian additions. Here we discuss general principles of small GTPase biology, survey the C. elegans complement of small GTPases and how they compare to their mammalian counterparts, and note atypical nematode members that do not fall into discrete subfamilies. We do not discuss the multitude of other proteins with catalytic guanosine triphosphatase domains that fall outside the small GTPase/Ras superfamily.
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PMID:Small GTPases. 2721 82

Plants' reaction to underground microorganisms is complex as sessile nature of plants compels them to prioritize their responses to diverse microorganisms both pathogenic and symbiotic. Roots of important crops are directly exposed to diverse microorganisms, but investigations involving root pathogens are significantly less. Thus, more studies involving root pathogens and their target crops are necessitated to enrich the understanding of underground interactions. Present study reported the molecular complexities in chickpea during Fusarium oxysporum f. sp. ciceri Race 1 (Foc1) infection. Transcriptomic dissections using RNA-seq showed significantly differential expression of molecular transcripts between infected and control plants of both susceptible and resistant genotypes. Radar plot analyses showed maximum expressional undulations after infection in both susceptible and resistant plants. Gene ontology and functional clustering showed large number of transcripts controlling basic metabolism of plants. Network analyses demonstrated defense components like peptidyl cis/trans isomerase, MAP kinase, beta 1,3 glucanase, serine threonine kinase, patatin like protein, lactolylglutathione lyase, coproporphyrinogen III oxidase, sulfotransferases; reactive oxygen species regulating components like respiratory burst oxidase, superoxide dismutases, cytochrome b5 reductase, glutathione reductase, thioredoxin reductase, ATPase; metabolism regulating components, myo inositol phosphate, carboxylate synthase; transport related gamma tonoplast intrinsic protein, and structural component, ubiquitins to serve as important nodals of defense signaling network. These nodal molecules probably served as hub controllers of defense signaling. Functional characterization of these hub molecules would not only help in developing better understanding of chickpea-Foc1 interaction but also place them as promising candidates for resistance management programs against vascular wilt of legumes.
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PMID:Transcriptomic dissection reveals wide spread differential expression in chickpea during early time points of Fusarium oxysporum f. sp. ciceri Race 1 attack. 2854 79

Intracellular calcium (Ca²⁺⁾ is a critical coordinator of various aspects of cellular physiology. It is increasingly apparent that changes in cellular Ca²⁺ dynamics contribute to the regulation of normal and pathological signal transduction that controls cell growth and survival. Aberrant perturbations in Ca²⁺ homeostasis have been implicated in a range of pathological conditions, such as cardiovascular diseases, diabetes, tumorigenesis and steatosis hepatitis. Intracellular Ca²⁺ concentrations are therefore tightly regulated by a number of Ca²⁺ handling enzymes, proteins, channels and transporters located in the plasma membrane and in Ca²⁺ storage organelles, which work in concert to fine tune a temporally and spatially precise Ca²⁺ signal. Chief amongst them is the sarco/endoplasmic reticulum (SR/ER) Ca²⁺ ATPase pump (SERCA) which actively re-accumulates released Ca²⁺ back into the SR/ER, therefore maintaining Ca²⁺ homeostasis. There are at least 14 different SERCA isoforms encoded by three ATP2A1-3 genes whose expressions are species- and tissue-specific. Altered SERCA expression and activity results in cellular malignancy and induction of ER stress and ER stress-associated apoptosis. The role of SERCA misregulation in the control of apoptosis in various cell types and disease setting with prospective therapeutic implications is the focus of this review. Ca²⁺ is a double edge sword for both life as well as death, and current experimental evidence supports a model in which Ca²⁺ homeostasis and SERCA activity represent a nodal point that controls cell survival. Pharmacological or genetic targeting of this axis constitutes an incredible therapeutic potential to treat different diseases sharing similar biological disorders.
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PMID:SERCA control of cell death and survival. 2874 51

Two features common to diverse sick excitable cells are "leaky" Nav channels and bleb damage-damaged membranes. The bleb damage, we have argued, causes a channel kinetics based "leakiness." Recombinant (node of Ranvier type) Nav1.6 channels voltage-clamped in mechanically-blebbed cell-attached patches undergo a damage intensity dependent kinetic change. Specifically, they experience a coupled hyperpolarizing (left) shift of the activation and inactivation processes. The biophysical observations on Nav1.6 currents formed the basis of Nav-Coupled Left Shift (Nav-CLS) theory. Node of Ranvier excitability can be modeled with Nav-CLS imposed at varying LS intensities and with varying fractions of total nodal membrane affected. Mild damage from which sick excitable cells might recover is of most interest pathologically. Accordingly, Na⁺/K⁺ ATPase (pump) activity was included in the modeling. As we described more fully in our other recent reviews, Nav-CLS in nodes with pumps proves sufficient to predict many of the pathological excitability phenomena reported for sick excitable cells. This review explains how the model came about and outlines how we have used it. Briefly, we direct the reader to studies in which Nav-CLS is being implemented in larger scale models of damaged excitable tissue. For those who might find it useful for teaching or research purposes, we coded the Nav-CLS/node of Ranvier model (with pumps) in NEURON. We include, here, the resulting "Regimes" plot of classes of excitability dysfunction.
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PMID:Calculating the Consequences of Left-Shifted Nav Channel Activity in Sick Excitable Cells. 2903 Jul 12

In this study, the first complete mitogenome of Andrenidae, namely Andrena camellia, is newly sequenced. It includes 13 protein-coding (PCG) genes, 22 transfer RNA (rRNA) genes, two ribosomal RNA (tRNA) genes, and a control region. Among PCGs, high conservation is observed in cytochrome oxidase genes with cox1 exhibits the highest conservation. Conversely, NADH dehydrogenase and ATPase subunit genes are more variable with atp8 presents the maximal variation. Comparison of the gene order indicates complex rearrangement in bees. Most of the rearranged events are located in the tRNA clusters of trnI-trnQ-trnM, trnW-trnC-trnY, and trnA-trnR-trnN-trnS1-trnE-trnF. Furthermore, we present the most comprehensive mitochondrial phylogeny of bee families. The monophyly of each family and the long-tongued bees is highly supported. However, short-tongued bees are inferred as paraphyletic relative to the sister relationship between Melittidae and other bee families. Furthermore, to improve the resolution of phylogeny, various datasets and analytical approaches are performed. It is indicated that datasets including third codons of PCGs facilitate to produce identical topology and higher nodal support. The tRNA genes that have typical cloverleaf secondary structures also exhibit similar positive effects. However, rRNAs present poor sequence alignment and distinct substitution saturation, which result in negative effects on both tree topology and nodal support. In addition, Gblocks treatment can increase the congruence of topologies, but has opposite effects on nodal support between the two inference methods of maximum likelihood and Bayesian inference.
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PMID:Phylogenetic analysis of the mitochondrial genomes in bees (Hymenoptera: Apoidea: Anthophila). 3009 91


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