scholarly journals Global analysis of protein arginine methylation

2021 ◽  
Author(s):  
Fangrong Zhang ◽  
Jakob Kerbl-Knapp ◽  
Maria J. Rodriguez Colman ◽  
Therese Macher ◽  
Nemanja Vujić ◽  
...  
Keyword(s):  
Global Analysis ◽  
High Sensitivity ◽  
Quantitative Information ◽  
Arginine Methylation ◽  
Cellular Functions ◽  
Physiological Processes ◽  
Mouse Tissues ◽  
Wide Range ◽  
Health And Disease ◽  
Protein Arginine Methylation

SummaryQuantitative information about the levels and dynamics of post-translational modifications (PTMs) is critical for an understanding of cellular functions. Protein arginine methylation (ArgMet) is an important subclass of PTMs and is involved in a plethora of (patho)physiological processes. However, due to the lack of methods for global analysis of ArgMet, the link between ArgMet levels, dynamics and (patho)physiology remains largely unknown. We utilized the high sensitivity and robustness of Nuclear Magnetic Resonance (NMR) spectroscopy to develop a general method for the quantification of global protein ArgMet. Our NMR-based approach enables the detection of protein ArgMet in purified proteins, cells, organoids, and mouse tissues. We demonstrate that the process of ArgMet is a highly prevalent PTM and can be modulated by small-molecule inhibitors and metabolites and changes in cancer and during ageing. Thus, our approach enables to address a wide range of biological questions related to ArgMet in health and disease.Graphical Abstract

scholarly journals Role of Insulin in Health and Disease: An Update

2021 ◽  
Vol 22 (12) ◽  
pp. 6403
Author(s):  
Md Saidur Rahman ◽  
Khandkar Shaharina Hossain ◽  
Sharnali Das ◽  
Sushmita Kundu ◽  
Elikanah Olusayo Adegoke ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Basic Research ◽  
Future Research ◽  
Protective Effects ◽  
Glucose Levels ◽  
Physiological Processes ◽  
Blood Glucose Levels ◽  
Wide Range ◽  
Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

scholarly journals Epigenetic Modulation of Vasopressin Expression in Health and Disease

2021 ◽  
Vol 22 (17) ◽  
pp. 9415
Author(s):  
Bibiána Török ◽  
Csilla Lea Fazekas ◽  
Adrienn Szabó ◽  
Dóra Zelena
Keyword(s):  
Social Interactions ◽  
Central Effect ◽  
Stress Axis ◽  
Epigenetic Changes ◽  
Physiological Processes ◽  
Micro Rnas ◽  
Wide Range ◽  
Behavior Learning ◽  
Health And Disease ◽  
Epigenetic Modulation

Vasopressin is a ubiquitous molecule playing an important role in a wide range of physiological processes thereby implicated in the pathomechanism of many disorders. Its effect is well characterized through V2 receptors, which regulates the water resorption in kidney, while its vasoconstrictory effect through V1a receptor also received a lot of attention in the maintenance of blood pressure during shock. However, the most striking is its central effect both through the V1b receptors in stress-axis regulation as well as through V1a receptors regulating many aspects of our behavior (e.g., social behavior, learning and memory). Vasopressin has been implicated in the development of depression, due to its connection with chronic stress, as well as schizophrenia because of its involvement in social interactions and memory processes. Epigenetic changes may also play a role in the development of these disorders. The possible mechanism includes DNA methylation, histone modification and/or micro RNAs, and these possible regulations will be in the focus of our present review.

scholarly journals A Review on Adducin from Functional to Pathological Mechanisms: Future Direction in Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Karrie Mei-Yee Kiang ◽  
Gilberto Ka-Kit Leung
Keyword(s):  
Membrane Skeleton ◽  
Cellular Functions ◽  
Structural Formation ◽  
Physical Support ◽  
Calcium Calmodulin Dependent ◽  
Physiological Processes ◽  
Kinase C ◽  
Wide Range ◽  
Future Direction ◽  
Cellular Compartments

Adducin (ADD) is a family of membrane skeleton proteins including ADD1, ADD2, and ADD3 that are encoded by distinct genes on different chromosomes. Adducin is primarily responsible for the assembly of spectrin-actin network that provides physical support to the plasma membrane and mediates signal transduction in various cellular physiological processes upon regulation by protein kinase C-dependent and calcium/calmodulin-dependent pathways. Abnormal phosphorylation, genetic variations, and alternative splicing of adducin may contribute to alterations in cellular functions involved in pathogenic processes. These alterations are associated with a wide range of diseases including cancer. This paper begins with a discussion on how adducin partakes in the structural formation of membrane skeleton, its regulation, and related functional characteristics, followed by a review on the pathogenesis of hypertension, biliary atresia, and cancer with respect to increased disease susceptibility mediated by adducin polymorphism and/or dysregulation. Given the functional diversity of adducin in different cellular compartments, we aim to provide a knowledge base whereby its pathophysiological roles can be better understood. More importantly, we aim to provide novel insights that may be of significance in turning the adducin model to clinical application.

scholarly journals Global query on bacterial sirtuin CobB interactants reveals crosstalk with PRPP synthase Prs

2020 ◽  
Author(s):  
Beata M. Walter ◽  
Joanna Morcinek-Orłowska ◽  
Aneta Szulc ◽  
Andrew L. Lovering ◽  
Manuel Banzhaf ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Global Analysis ◽  
Stable Complex ◽  
Protein Protein Interactions ◽  
Cellular Functions ◽  
Nad Metabolism ◽  
E Coli ◽  
Nad Synthesis ◽  
Wide Range

AbstractProtein lysine acetylation regulates a wide range of cellular functions. It is controlled by a family of NAD-dependent protein deacetylases called sirtuins. In eukaryotes, sirtuins activity is coupled to spatiotemporally-controlled NAD+ level, whereas the mechanism of their regulation in bacteria is less clear. E. coli possesses a single sirtuin – CobB. However, it is unclear how CobB activity is coupled to NAD+ metabolism. In this work we show that this coordination is achieved in E. coli cells through a CobB interaction with PRPP synthase Prs, an enzyme necessary for NAD+ synthesis. Employing global analysis of protein-protein interactions formed by CobB, we demonstrate that it forms a stable complex with Prs. This assembly stimulates CobB deacetylase activity and partially protects it from inhibition by nicotinamide. We provide evidence that Prs acetylation is not necessary for CobB binding but affects the global acetylome in vivo. Our results show that CobB ameliorates Prs activity under conditions of Prs cofactors deficiency. Therefore, we propose that CobB-Prs crosstalk orchestrates the NAD+ metabolism and protein acetylation in response to environmental cues.

scholarly journals METALLOTHIONEINS AS SENSORS AND CONTROLS EXCHANGE OF METALS IN THE CELLS

2014 ◽  
Vol 13 (3) ◽  
pp. 91-99 ◽  
Author(s):  
V. A. Kutyakov ◽  
A. V. Salmina
Keyword(s):  
Stress Factors ◽  
Special Role ◽  
Cellular Functions ◽  
Regulation Of Expression ◽  
Wide Range ◽  
Health And Disease ◽  
Pharmacology And Toxicology ◽  
Regulatory Functions ◽  
The Impact

The basic information on the classification, structure, induction and degradation, functions of the protein family – metallothionein (MT), including CNS in health and disease are presented in this review. It was found that four major isoforms of metallothionein perform different biological roles, are localized in dif- ferent tissues. Induction of MT is a universal reaction to the impact of a variety of stress factors. In recent years, understanding of the role of metallothioneins in metal homeostasis in the tissues in normal and pathological conditions have changed significantly. Notes polyfunctionality metallothioneins (transport of metal ions, maintaining redox reactions, tread, signal, modulated and regulatory functions) and their im- pact on basic cellular functions such as proliferation, differentiation, programmed cell death. Further- more, a special role is shown MT in the pathogenesis of cardiovascular, neurodegenerative and neoplastic disorders.Currently, these molecules are increasingly considered as potential targets for therapy of a wide range of diseases and the development of targeted approaches to the regulation of expression of MT – one of the promising areas of pharmacology and toxicology. Stressed the safety of metallothioneins as therapeutic agents.

Role of Caveolae and Caveolins in Health and Disease

2004 ◽  
Vol 84 (4) ◽  
pp. 1341-1379 ◽  
Author(s):  
Alex W. Cohen ◽  
Robert Hnasko ◽  
William Schubert ◽  
Michael P. Lisanti
Keyword(s):  
Signaling Molecules ◽  
Membrane Lipid ◽  
Scaffolding Proteins ◽  
Cellular Functions ◽  
Coated Pits ◽  
Caveolin 1 ◽  
Plasma Membrane Lipid ◽  
Wide Range ◽  
Health And Disease ◽  
Vesicular Transporters

Although they were discovered more than 50 years ago, caveolae have remained enigmatic plasmalemmal organelles. With their characteristic “flasklike” shape and virtually ubiquitous tissue distribution, these interesting structures have been implicated in a wide range of cellular functions. Similar to clathrin-coated pits, caveolae function as macromolecular vesicular transporters, while their unique lipid composition classifies them as plasma membrane lipid rafts, structures enriched in a variety of signaling molecules. The caveolin proteins (caveolin-1, -2, and -3) serve as the structural components of caveolae, while also functioning as scaffolding proteins, capable of recruiting numerous signaling molecules to caveolae, as well as regulating their activity. That so many signaling molecules and signaling cascades are regulated by an interaction with the caveolins provides a paradigm by which numerous disease processes may be affected by ablation or mutation of these proteins. Indeed, studies in caveolin-deficient mice have implicated these structures in a host of human diseases, including diabetes, cancer, cardiovascular disease, atherosclerosis, pulmonary fibrosis, and a variety of degenerative muscular dystrophies. In this review, we provide an in depth summary regarding the mechanisms by which caveolae and caveolins participate in human disease processes.

scholarly journals SumSec: Accurate Prediction of Sumoylation Sites Using Predicted Secondary Structure

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3260 ◽  
Author(s):  
Abdollah Dehzangi ◽  
Yosvany López ◽  
Ghazaleh Taherzadeh ◽  
Alok Sharma ◽  
Tatsuhiko Tsunoda
Keyword(s):  
Amino Acids ◽  
Secondary Structure ◽  
High Sensitivity ◽  
Underlying Mechanism ◽  
Structural Features ◽  
Post Translational Modification ◽  
Cellular Functions ◽  
Sumoylation Site ◽  
Translation Process ◽  
Wide Range

Post Translational Modification (PTM) is defined as the modification of amino acids along the protein sequences after the translation process. These modifications significantly impact on the functioning of proteins. Therefore, having a comprehensive understanding of the underlying mechanism of PTMs turns out to be critical in studying the biological roles of proteins. Among a wide range of PTMs, sumoylation is one of the most important modifications due to its known cellular functions which include transcriptional regulation, protein stability, and protein subcellular localization. Despite its importance, determining sumoylation sites via experimental methods is time-consuming and costly. This has led to a great demand for the development of fast computational methods able to accurately determine sumoylation sites in proteins. In this study, we present a new machine learning-based method for predicting sumoylation sites called SumSec. To do this, we employed the predicted secondary structure of amino acids to extract two types of structural features from neighboring amino acids along the protein sequence which has never been used for this task. As a result, our proposed method is able to enhance the sumoylation site prediction task, outperforming previously proposed methods in the literature. SumSec demonstrated high sensitivity (0.91), accuracy (0.94) and MCC (0.88). The prediction accuracy achieved in this study is 21% better than those reported in previous studies. The script and extracted features are publicly available at: https://github.com/YosvanyLopez/SumSec.

scholarly journals Quantifying Mitochondrial Dynamics in Patient Fibroblasts with Multiple Developmental Defects and Mitochondrial Disorders

2021 ◽  
Vol 22 (12) ◽  
pp. 6263
Author(s):  
Ajibola B. Bakare ◽  
Julienne Daniel ◽  
Joshua Stabach ◽  
Anapaula Rojas ◽  
Austin Bell ◽  
...  
Keyword(s):  
Cell Lines ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Disorders ◽  
Cellular Functions ◽  
Developmental Defects ◽  
Mitochondrial Structure ◽  
Wide Range ◽  
Health And Disease ◽  
Diseased State ◽  
Comprehensive Study

Mitochondria are dynamic organelles that undergo rounds of fission and fusion and exhibit a wide range of morphologies that contribute to the regulation of different signaling pathways and various cellular functions. It is important to understand the differences between mitochondrial structure in health and disease so that therapies can be developed to maintain the homeostatic balance of mitochondrial dynamics. Mitochondrial disorders are multisystemic and characterized by complex and variable clinical pathologies. The dynamics of mitochondria in mitochondrial disorders is thus worthy of investigation. Therefore, in this study, we performed a comprehensive analysis of mitochondrial dynamics in ten patient-derived fibroblasts containing different mutations and deletions associated with various mitochondrial disorders. Our results suggest that the most predominant morphological signature for mitochondria in the diseased state is fragmentation, with eight out of the ten cell lines exhibiting characteristics consistent with fragmented mitochondria. To our knowledge, this is the first comprehensive study that quantifies mitochondrial dynamics in cell lines with a wide array of developmental and mitochondrial disorders. A more thorough analysis of the correlations between mitochondrial dynamics, mitochondrial genome perturbations, and bioenergetic dysfunction will aid in identifying unique morphological signatures of various mitochondrial disorders in the future.

scholarly journals Global analysis of protein arginine methylation

2021 ◽  
Vol 1 (2) ◽  
pp. 100016
Author(s):  
Fangrong Zhang ◽  
Jakob Kerbl-Knapp ◽  
Maria J. Rodriguez Colman ◽  
Andreas Meinitzer ◽  
Therese Macher ◽  
...  
Keyword(s):  
Global Analysis ◽  
Arginine Methylation ◽  
Protein Arginine Methylation
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