How Viruses Use the VCP/p97 ATPase Molecular Machine

Viruses are obligate intracellular parasites that are dependent on host factors for their replication. One such host protein, p97 or the valosin-containing protein (VCP), is a highly conserved AAA ATPase that facilitates replication of diverse RNA- and DNA-containing viruses. The wide range of cellular functions attributed to this ATPase is consistent with its participation in multiple steps of the virus life cycle from entry and uncoating to viral egress. Studies of VCP/p97 interactions with viruses will provide important information about host processes and cell biology, but also viral strategies that take advantage of these host functions. The critical role of p97 in viral replication might be exploited as a target for development of pan-antiviral drugs that exceed the capability of virus-specific vaccines or therapeutics.

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Development of cancer metabolism as a therapeutic target: new pathways, patient studies, stratification and combination therapy

British Journal of Cancer ◽

10.1038/s41416-019-0666-4 ◽

2019 ◽

Vol 122 (1) ◽

pp. 1-3 ◽

Cited By ~ 4

Author(s):

Adrian L. Harris

Keyword(s):

Metabolic Pathways ◽

Trial Design ◽

Cancer Metabolism ◽

Aerobic Glycolysis ◽

Critical Role ◽

Therapeutic Approaches ◽

Preclinical Models ◽

Wide Range ◽

Patient Studies

AbstractCancer metabolism has undergone a resurgence in the last decade, 70 years after Warburg described aerobic glycolysis as a feature of cancer cells. A wide range of techniques have elucidated the complexity and heterogeneity in preclinical models and clinical studies. What emerges are the large differences between tissues, tumour types and intratumour heterogeneity. However, synergies with inhibition of metabolic pathways have been found for many drugs and therapeutic approaches, and a critical role of window studies and translational trial design is key to success.

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Role of Platelet-Activating Factor in Cardiovascular Pathophysiology

Physiological Reviews ◽

10.1152/physrev.2000.80.4.1669 ◽

2000 ◽

Vol 80 (4) ◽

pp. 1669-1699 ◽

Cited By ~ 245

Author(s):

Giuseppe Montrucchio ◽

Giuseppe Alloatti ◽

Giovanni Camussi

Keyword(s):

Cardiovascular System ◽

Cell Biology ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Critical Role ◽

Experimental Studies ◽

Platelet Activating Factor ◽

Biologically Active ◽

Endothelial Cell Migration

Platelet-activating factor (PAF) is a phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglycerides. PAF acts via a specific receptor that is coupled with a G protein, which activates a phosphatidylinositol-specific phospholipase C. In this review we focus on the aspects that are more relevant for the cell biology of the cardiovascular system. The in vitro studies provided evidence for a role of PAF both as intercellular and intracellular messenger involved in cell-to-cell communication. In the cardiovascular system, PAF may have a role in embryogenesis because it stimulates endothelial cell migration and angiogenesis and may affect cardiac function because it exhibits mechanical and electrophysiological actions on cardiomyocytes. Moreover, PAF may contribute to modulation of blood pressure mainly by affecting the renal vascular circulation. In pathological conditions, PAF has been involved in the hypotension and cardiac dysfunctions occurring in various cardiovascular stress situations such as cardiac anaphylaxis and hemorrhagic, traumatic, and septic shock syndromes. In addition, experimental studies indicate that PAF has a critical role in the development of myocardial ischemia-reperfusion injury. Indeed, PAF cooperates in the recruitment of leukocytes in inflamed tissue by promoting adhesion to the endothelium and extravascular transmigration of leukocytes. The finding that human heart can produce PAF, expresses PAF receptor, and is sensitive to the negative inotropic action of PAF suggests that this mediator may have a role also in human cardiovascular pathophysiology.

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Wildlife management and the debate on the ethics of animal use. II. A challenge for the animal protection movement.

Pacific Conservation Biology ◽

10.1071/pc120081 ◽

2012 ◽

Vol 18 (2) ◽

pp. 81 ◽

Cited By ~ 9

Author(s):

Daniel Lunney

Keyword(s):

Wildlife Management ◽

Critical Role ◽

Animal Liberation ◽

Ethical Imperative ◽

Animal Protection ◽

Wide Range ◽

Animal Use

How people coexist and interact with animals has become an intensely debated issue in recent times, particularly with the rise of the animal protection movement following the publication of Peter Singer’s book Animal Liberation in 1975. This paper discusses some shortcomings of the philosophical positions taken in this complex debate. Singer has helped put animals on a new footing as a group that cannot morally be ignored, but his focus is mainly on individual, familiar animals that are used or abused by humans. The argument of this paper is that the ethics of managing wildlife hinges on a broader view of animals, and their contexts, than is apparent from Singer’s text. Wildlife managers aim to conserve populations of a wide range of species, and their habitats, but some mechanisms for achieving these aims, such as research and the control of invasive animals, are frequently opposed by elements of the animal protection movement. We need to adapt our attitude to animals, particularly wildlife, away from the traditional legacy of a few familiar species to embrace an ethic that is more ecological and relevant to Australian contexts. The case argued here has been to see the critical role of context — geographical, ecological, historical, relational — as a basis for a degree of reconciliation between conservation-oriented wildlife managers and the rising interest in the ethics of animal use. There is much to be gained for zoologists, wildlife managers and conservation biologists by framing key elements of their case in ethical arguments. Conversely, the challenge for those in the animal protection movement is to expand their philosophical ideas to include the ethical imperative of the conservation of populations of wildlife.

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The AAA+ ATPase p97, a cellular multitool

Biochemical Journal ◽

10.1042/bcj20160783 ◽

2017 ◽

Vol 474 (17) ◽

pp. 2953-2976 ◽

Cited By ~ 42

Author(s):

Lasse Stach ◽

Paul S. Freemont

Keyword(s):

Atp Hydrolysis ◽

Current Status ◽

Cellular Functions ◽

Aaa Atpase ◽

Cellular Processes ◽

Proteotoxic Stress ◽

Binding Domains ◽

Wide Range ◽

Aaa Atpases ◽

Substrate Proteins

The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes. A multitude of p97 cofactors have evolved which are essential to p97 function. Ubiquitin-interacting domains and p97-binding domains combine to form bi-functional cofactors, whose complexes with p97 enable the enzyme to interact with a wide range of ubiquitinated substrates. A set of mutations in p97 have been shown to cause the multisystem proteinopathy inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. In addition, p97 inhibition has been identified as a promising approach to provoke proteotoxic stress in tumors. In this review, we will describe the cellular processes governed by p97, how the cofactors interact with both p97 and its ubiquitinated substrates, p97 enzymology and the current status in developing p97 inhibitors for cancer therapy.

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Cytochemical methods for the localization of adenylate cyclase. A review and evaluation of the efficacy of the procedures.

Journal of Histochemistry & Cytochemistry ◽

10.1177/31.1.6187806 ◽

1983 ◽

Vol 31 (1) ◽

pp. 85-93 ◽

Cited By ~ 31

Author(s):

L S Cutler

Keyword(s):

Adenylate Cyclase ◽

Cyclic Nucleotides ◽

Cell Biology ◽

Enzyme System ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Cellular Functions ◽

Cytochemical Localization ◽

Biochemical Evaluation

The cytochemical procedures for localizing adenylate cyclase have been a source of controversy since their introduction. The importance of cyclic adenosine monophosphate (AMP), the product of adenylate cyclase's action on adenosine triphosphate (ATP), in cell biology is clear. Thus, the ability to localize this enzyme system reliably is an important tool in the study of various cellular functions. This report reviews the literature and presents a biochemical evaluation of the methods for localizing adenylate cyclase. The review and data presented serve to clarify many of the controversies surrounding this important cytochemical procedure. It is evident that although there are problems associated with localizing the enzyme, several valid procedures are currently available for the cytochemical localization of adenylate cyclase. In using these procedures, the effects of fixation and the capture agent on adenylate cyclase activity in the particular tissue being studied should be considered. Only repurified adenylyl imidodiphosphate [App(NH)p] should be used in the incubation medium. If care is taken, the use of these techniques can be of great value in the continued study of the role of cyclic nucleotides in cell biology.

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Ubiquilin Networking in Cancers

Cancers ◽

10.3390/cancers12061586 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1586

Author(s):

Salinee Jantrapirom ◽

Luca Lo Piccolo ◽

Dumnoensun Pruksakorn ◽

Saranyapin Potikanond ◽

Wutigri Nimlamool

Keyword(s):

Cell Cycle ◽

Genetic Variants ◽

Epithelial Mesenchymal Transition ◽

Excision Repair ◽

Cancer Therapies ◽

Cellular Functions ◽

Mesenchymal Transition ◽

Wide Range ◽

Nucleotide Excision

Ubiquilins or UBQLNs, members of the ubiquitin-like and ubiquitin-associated domain (UBL-UBA) protein family, serve as adaptors to coordinate the degradation of specific substrates via both proteasome and autophagy pathways. The UBQLN substrates reveal great diversity and impact a wide range of cellular functions. For decades, researchers have been attempting to uncover a puzzle and understand the role of UBQLNs in human cancers, particularly in the modulation of oncogene’s stability and nucleotide excision repair. In this review, we summarize the UBQLNs’ genetic variants that are associated with the most common cancers and also discuss their reliability as a prognostic marker. Moreover, we provide an overview of the UBQLNs networks that are relevant to cancers in different ways, including cell cycle, apoptosis, epithelial-mesenchymal transition, DNA repairs and miRNAs. Finally, we include a future prospective on novel ubiquilin-based cancer therapies.

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LSD1, a double-edged sword, confers dynamic chromatin regulation but commonly promotes aberrant cell growth

F1000Research ◽

10.12688/f1000research.12169.1 ◽

2017 ◽

Vol 6 ◽

pp. 2016 ◽

Cited By ~ 13

Author(s):

Meghan M Kozub ◽

Ryan M Carr ◽

Gwen L Lomberk ◽

Martin E Fernandez-Zapico

Keyword(s):

Gene Expression ◽

Chromatin Remodeling ◽

Cellular Differentiation ◽

Critical Role ◽

Histone Demethylase ◽

Epigenetic Changes ◽

Lysine Specific Demethylase ◽

Wide Range ◽

Histone Modifying Enzymes

Histone-modifying enzymes play a critical role in chromatin remodeling and are essential for influencing several genome processes such as gene expression and DNA repair, replication, and recombination. The discovery of lysine-specific demethylase 1 (LSD1), the first identified histone demethylase, dramatically revolutionized research in the field of epigenetics. LSD1 plays a pivotal role in a wide range of biological operations, including development, cellular differentiation, embryonic pluripotency, and disease (for example, cancer). This mini-review focuses on the role of LSD1 in chromatin regulatory complexes, its involvement in epigenetic changes throughout development, and its importance in physiological and pathological processes.

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The Role of Sirtuins in Kidney Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms21186686 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6686

Author(s):

Yu Ah Hong ◽

Ji Eun Kim ◽

Minjee Jo ◽

Gang-Jee Ko

Keyword(s):

Histone Deacetylases ◽

Energy Homeostasis ◽

Molecular Mechanisms ◽

Kidney Diseases ◽

Expression Profiles ◽

Kidney Injury ◽

Class Iii ◽

Cellular Functions ◽

Wide Range

Sirtuins (SIRTs) are class III histone deacetylases (HDACs) that play important roles in aging and a wide range of cellular functions. Sirtuins are crucial to numerous biological processes, including proliferation, DNA repair, mitochondrial energy homeostasis, and antioxidant activity. Mammals have seven different sirtuins, SIRT1–7, and the diverse biological functions of each sirtuin are due to differences in subcellular localization, expression profiles, and cellular substrates. In this review, we summarize research advances into the role of sirtuins in the pathogenesis of various kidney diseases including acute kidney injury, diabetic kidney disease, renal fibrosis, and kidney aging along with the possible underlying molecular mechanisms. The available evidence indicates that sirtuins have great potential as novel therapeutic targets for the prevention and treatment of kidney diseases.

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What Neuroscientific Studies Tell Us about Inhibition of Return

Vision ◽

10.3390/vision3040058 ◽

2019 ◽

Vol 3 (4) ◽

pp. 58 ◽

Cited By ~ 2

Author(s):

Jason Satel ◽

Nicholas R. Wilson ◽

Raymond M. Klein

Keyword(s):

Inhibition Of Return ◽

Brain Activity ◽

Critical Role ◽

Direct Methods ◽

Brain Structures ◽

Developmental Studies ◽

Unit Recording ◽

Wide Range ◽

Lesion Studies

An inhibitory aftermath of orienting, inhibition of return (IOR), has intrigued scholars since its discovery about 40 years ago. Since then, the phenomenon has been subjected to a wide range of neuroscientific methods and the results of these are reviewed in this paper. These include direct manipulations of brain structures (which occur naturally in brain damage and disease or experimentally as in TMS and lesion studies) and measurements of brain activity (in humans using EEG and fMRI and in animals using single unit recording). A variety of less direct methods (e.g., computational modeling, developmental studies, etc.) have also been used. The findings from this wide range of methods support the critical role of subcortical and cortical oculomotor pathways in the generation and nature of IOR.

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