Deubiquitylases From Genes to Organism

2013 ◽  
Vol 93 (3) ◽  
pp. 1289-1315 ◽  
Author(s):  
Michael J. Clague ◽  
Igor Barsukov ◽  
Judy M. Coulson ◽  
Han Liu ◽  
Daniel J. Rigden ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Large Family ◽  
Tissue Expression ◽  
Cell Physiology ◽  
Functional Roles ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Copy Numbers ◽  
Free Ubiquitin

Ubiquitylation is a major posttranslational modification that controls most complex aspects of cell physiology. It is reversed through the action of a large family of deubiquitylating enzymes (DUBs) that are emerging as attractive therapeutic targets for a number of disease conditions. Here, we provide a comprehensive analysis of the complement of human DUBs, indicating structural motifs, typical cellular copy numbers, and tissue expression profiles. We discuss the means by which specificity is achieved and how DUB activity may be regulated. Generically DUB catalytic activity may be used to 1) maintain free ubiquitin levels, 2) rescue proteins from ubiquitin-mediated degradation, and 3) control the dynamics of ubiquitin-mediated signaling events. Functional roles of individual DUBs from each of five subfamilies in specific cellular processes are highlighted with an emphasis on those linked to pathological conditions where the association is supported by whole organism models. We then specifically consider the role of DUBs associated with protein degradative machineries and the influence of specific DUBs upon expression of receptors and channels at the plasma membrane.

MicroRNAs as Biomarker for Breast Cancer

2020 ◽  
Vol 20 (10) ◽  
pp. 1597-1610 ◽  
Author(s):  
Taru Aggarwal ◽  
Ridhima Wadhwa ◽  
Riya Gupta ◽  
Keshav Raj Paudel ◽  
Trudi Collet ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Association Studies ◽  
Large Family ◽  
Breast Cancer Diagnosis ◽  
Cell Multiplication ◽  
Cell Physiology ◽  
Gene Transcript ◽  
Genome Wide Association Studies ◽  
Non Coding Rnas

Regardless of advances in detection and treatment, breast cancer affects about 1.5 million women all over the world. Since the last decade, genome-wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause a disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus to study the role of microRNAs in breast cancer.

scholarly journals The Pleiotropic Function of Human Sirtuins as Modulators of Metabolic Pathways and Viral Infections

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 460
Author(s):  
Mohammed Hamed Alqarni ◽  
Ahmed Ibrahim Foudah ◽  
Magdy Mohamed Muharram ◽  
Nikolaos E. Labrou
Keyword(s):  
Metabolic Pathways ◽  
Histone Deacetylases ◽  
Viral Infections ◽  
Cell Physiology ◽  
Functional Roles ◽  
Regulatory Processes ◽  
Complex Functions ◽  
Natural Polyphenol ◽  
Antiviral Targets

Sirtuins (SIRTs) are nicotinamide adenine dinucleotide-dependent histone deacetylases that incorporate complex functions in the mechanisms of cell physiology. Mammals have seven distinct members of the SIRT family (SIRT1-7), which play an important role in a well-maintained network of metabolic pathways that control and adapt the cell to the environment, energy availability and cellular stress. Until recently, very few studies investigated the role of SIRTs in modulating viral infection and progeny. Recent studies have demonstrated that SIRT1 and SIRT2 are promising antiviral targets because of their specific connection to numerous metabolic and regulatory processes affected during infection. In the present review, we summarize some of the recent progress in SIRTs biochemistry and their emerging function as antiviral targets. We also discuss the potential of natural polyphenol-based SIRT modulators to control their functional roles in several diseases including viral infections.

scholarly journals The Role of Prokineticin 2 in Oxidative Stress and in Neuropathological Processes

2021 ◽  
Vol 12 ◽  
Author(s):  
Roberta Lattanzi ◽  
Cinzia Severini ◽  
Daniela Maftei ◽  
Luciano Saso ◽  
Aldo Badiani
Keyword(s):  
Pain Perception ◽  
G Protein Coupled Receptors ◽  
Cellular Processes ◽  
Prokineticin 2 ◽  
Physiological Processes ◽  
Pathological Conditions ◽  
Double Function ◽  
The Central Nervous System ◽  
G Protein Coupled

The prokineticin (PK) family, prokineticin 1 and Bv8/prokineticin 2 (PROK2), initially discovered as regulators of gastrointestinal motility, interacts with two G protein-coupled receptors, PKR1 and PKR2, regulating important biological functions such as circadian rhythms, metabolism, angiogenesis, neurogenesis, muscle contractility, hematopoiesis, immune response, reproduction and pain perception. PROK2 and PK receptors, in particular PKR2, are widespread distributed in the central nervous system, in both neurons and glial cells. The PROK2 expression levels can be increased by a series of pathological insults, such as hypoxia, reactive oxygen species, beta amyloid and excitotoxic glutamate. This suggests that the PK system, participating in different cellular processes that cause neuronal death, can be a key mediator in neurological/neurodegenerative diseases. While many PROK2/PKRs effects in physiological processes have been documented, their role in neuropathological conditions is not fully clarified, since PROK2 can have a double function in the mechanisms underlying to neurodegeneration or neuroprotection. Here, we briefly outline the latest findings on the modulation of PROK2 and its cognate receptors following different pathological insults, providing information about their opposite neurotoxic and neuroprotective role in different pathological conditions.

scholarly journals Mitochondria, pattern recognition receptors and autophagy under physiological and pathological conditions, including viral infections

2021 ◽  
Author(s):  
Paulina Niedźwiedzka-Rystwej ◽  
Dominika Bębnowska ◽  
Roman Kołacz ◽  
Wiesław Deptuła
Keyword(s):  
Pattern Recognition ◽  
Viral Infections ◽  
Apoptotic Cell ◽  
Pattern Recognition Receptors ◽  
The Body ◽  
The Other ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Other Hand

Research on the health of mammals invariably shows how dynamic immunology is and how the role of many elements and immune processes of the macroorganism, developed in the process of evolution in protecting against threats, including infections, is changing. Among these elements conditioning the homeostasis of the macroorganism are mitochondria, PRR receptors (pattern recognition receptors) and the phenomenon of autophagy. In the context of physiological and pathological states in the body, mitochondria perform various functions. The primary function of these organelles is to produce energy in the cell, but on the other hand, they are heavily involved in various cellular processes, including ROS production and calcium homeostasis. They are largely involved in the activation of immune mechanisms during infectious and non-infectious conditions through mtDNA and the mitochondrial MAVS protein. Mitochondrial involvement has been also determined in PRR-related mechanisms as mtDNA has the ability to directly stimulate TLRs. On the other hand, mitochondria are also associated with apoptotic cell death and autophagy.

scholarly journals When the chains do not break: the role of USP10 in physiology and pathology

2020 ◽  
Vol 11 (12) ◽  
Author(s):  
Udayan Bhattacharya ◽  
Fiifi Neizer-Ashun ◽  
Priyabrata Mukherjee ◽  
Resham Bhattacharya
Keyword(s):  
Complex Formation ◽  
Molecular Mechanisms ◽  
Protein Homeostasis ◽  
Post Translational Modification ◽  
Intracellular Protein ◽  
Lysosomal Degradation ◽  
Life Activity ◽  
Cellular Processes ◽  
Pathological Conditions

AbstractDeubiquitination is now understood to be as important as its partner ubiquitination for the maintenance of protein half-life, activity, and localization under both normal and pathological conditions. The enzymes that remove ubiquitin from target proteins are called deubiquitinases (DUBs) and they regulate a plethora of cellular processes. DUBs are essential enzymes that maintain intracellular protein homeostasis by recycling ubiquitin. Ubiquitination is a post-translational modification where ubiquitin molecules are added to proteins thus influencing activation, localization, and complex formation. Ubiquitin also acts as a tag for protein degradation, especially by proteasomal or lysosomal degradation systems. With ~100 members, DUBs are a large enzyme family; the ubiquitin-specific peptidases (USPs) being the largest group. USP10, an important member of this family, has enormous significance in diverse cellular processes and many human diseases. In this review, we discuss recent studies that define the roles of USP10 in maintaining cellular function, its involvement in human pathologies, and the molecular mechanisms underlying its association with cancer and neurodegenerative diseases. We also discuss efforts to modulate USPs as therapy in these diseases.

scholarly journals Molecules and Mechanisms to Overcome Oxidative Stress Inducing Cardiovascular Disease in Cancer Patients

Life ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 105
Author(s):  
Francesco Sabbatino ◽  
Valeria Conti ◽  
Luigi Liguori ◽  
Giovanna Polcaro ◽  
Graziamaria Corbi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Disease ◽  
Ros Production ◽  
Oxygen Species ◽  
Physiological Conditions ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Detoxification Systems ◽  
Cancer Diseases

Reactive oxygen species (ROS) are molecules involved in signal transduction pathways with both beneficial and detrimental effects on human cells. ROS are generated by many cellular processes including mitochondrial respiration, metabolism and enzymatic activities. In physiological conditions, ROS levels are well-balanced by antioxidative detoxification systems. In contrast, in pathological conditions such as cardiovascular, neurological and cancer diseases, ROS production exceeds the antioxidative detoxification capacity of cells, leading to cellular damages and death. In this review, we will first describe the biology and mechanisms of ROS mediated oxidative stress in cardiovascular disease. Second, we will review the role of oxidative stress mediated by oncological treatments in inducing cardiovascular disease. Lastly, we will discuss the strategies that potentially counteract the oxidative stress in order to fight the onset and progression of cardiovascular disease, including that induced by oncological treatments.

scholarly journals Endogenous Mobilization of Mesenchymal Stromal Cells: A Pathway for Interorgan Communication?

2021 ◽  
Vol 8 ◽  
Author(s):  
Amandine Girousse ◽  
Maxime Mathieu ◽  
Quentin Sastourné-Arrey ◽  
Sylvie Monferran ◽  
Louis Casteilla ◽  
...  
Keyword(s):  
Communication Network ◽  
Adipose Tissue ◽  
Stromal Cells ◽  
Current Knowledge ◽  
Adipose Stromal Cells ◽  
Maintenance And Repair ◽  
Beneficial Effects ◽  
Cellular Processes ◽  
Pathological Conditions

To coordinate specialized organs, inter-tissue communication appeared during evolution. Consequently, individual organs communicate their states via a vast interorgan communication network (ICN) made up of peptides, proteins, and metabolites that act between organs to coordinate cellular processes under homeostasis and stress. However, the nature of the interorgan signaling could be even more complex and involve mobilization mechanisms of unconventional cells that are still poorly described. Mesenchymal stem/stromal cells (MSCs) virtually reside in all tissues, though the biggest reservoir discovered so far is adipose tissue where they are named adipose stromal cells (ASCs). MSCs are thought to participate in tissue maintenance and repair since the administration of exogenous MSCs is well known to exert beneficial effects under several pathological conditions. However, the role of endogenous MSCs is barely understood. Though largely debated, the presence of circulating endogenous MSCs has been reported in multiple pathophysiological conditions, but the significance of such cell circulation is not known and therapeutically untapped. In this review, we discuss current knowledge on the circulation of native MSCs, and we highlight recent findings describing MSCs as putative key components of the ICN.

scholarly journals The Mitochondrial Citrate Carrier SLC25A1/CIC and the Fundamental Role of Citrate in Cancer, Inflammation and Beyond

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 141
Author(s):  
Rami Mosaoa ◽  
Anna Kasprzyk-Pawelec ◽  
Harvey R. Fernandez ◽  
Maria Laura Avantaggiati
Keyword(s):  
Large Family ◽  
Mechanisms Of Action ◽  
Human Diseases ◽  
Fundamental Function ◽  
Acetyl Coenzyme A ◽  
Pathological Conditions ◽  
Epigenetic Modifier ◽  
Cancer Inflammation ◽  
Mitochondrial Transporters

The mitochondrial citrate/isocitrate carrier, CIC, has been shown to play an important role in a growing list of human diseases. CIC belongs to a large family of nuclear-encoded mitochondrial transporters that serve the fundamental function of allowing the transit of ions and metabolites through the impermeable mitochondrial membrane. Citrate is central to mitochondrial metabolism and respiration and plays fundamental activities in the cytosol, serving as a metabolic substrate, an allosteric enzymatic regulator and, as the source of Acetyl-Coenzyme A, also as an epigenetic modifier. In this review, we highlight the complexity of the mechanisms of action of this transporter, describing its involvement in human diseases and the therapeutic opportunities for targeting its activity in several pathological conditions.

scholarly journals Emerging Roles of Extracellular Vesicles in the Central Nervous System: Physiology, Pathology, and Therapeutic Perspectives

2021 ◽  
Vol 15 ◽  
Author(s):  
Yadaly Gassama ◽  
Alexandre Favereaux
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
The Central Nervous System ◽  
System Physiology ◽  
The Brain

Extracellular vesicles or EVs are secreted by most, if not all, eukaryote cell types and recaptured by neighboring or distant cells. Their cargo, composed of a vast diversity of proteins, lipids, and nucleic acids, supports the EVs’ inter-cellular communication. The role of EVs in many cellular processes is now well documented both in physiological and pathological conditions. In this review, we focus on the role of EVs in the central nervous system (CNS) in physiological as well as pathological conditions such as neurodegenerative diseases or brain cancers. We also discuss the future of EVs in clinical research, in particular, their value as biomarkers as well as innovative therapeutic agents. While an increasing number of studies reveal EV research as a promising field, progress in the standardization of protocols and innovation in analysis as well as in research tools is needed to make a breakthrough in our understanding of their impact in the pathophysiology of the brain.

The ubiquitin-proteasome system in cardiac physiology and pathology

2006 ◽  
Vol 291 (1) ◽  
pp. H1-H19 ◽  
Author(s):  
Saul R. Powell
Keyword(s):  
Protein Turnover ◽  
Protein Quality ◽  
Ubiquitin Proteasome System ◽  
Intracellular Protein ◽  
Cellular Processes ◽  
Pathological Conditions ◽  
Intracellular Protein Degradation ◽  
Ubiquitin Proteasome ◽  
Protein Ligases

The ubiquitin-proteasome system (UPS) is the major nonlysosomal pathway for intracellular protein degradation, generally requiring a covalent linkage of one or more chains of polyubiquitins to the protein intended for degradation. It has become clear that the UPS plays major roles in regulating many cellular processes, including the cell cycle, immune responses, apoptosis, cell signaling, and protein turnover under normal and pathological conditions, as well as in protein quality control by removal of damaged, oxidized, and/or misfolded proteins. This review will present an overview of the structure, biochemistry, and physiology of the UPS with emphasis on its role in the heart, if known. In addition, evidence will be presented supporting the role of certain muscle-specific ubiquitin protein ligases, key regulatory components of the UPS, in regulation of sarcomere protein turnover and cardiomyocyte size and how this might play a role in induction of the hypertrophic phenotype. Moreover, this review will present the evidence suggesting that proteasomal dysfunction may play a role in cardiac pathologies such as myocardial ischemia, congestive heart failure, and myofilament-related and idiopathic-dilated cardiomyopathies, as well as cardiomyocyte loss in the aging heart. Finally, certain pitfalls of proteasome studies will be described with the intent of providing investigators with enough information to avoid these problems. This review should provide current investigators in the field with an up-to-date analysis of the literature and at the same time provide an impetus for new investigators to enter this important and rapidly changing area of research.

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