Development of Ubiquitin Tools for Studies of Complex Ubiquitin Processing Protein Machines

2020 ◽  
Vol 23 (23) ◽  
pp. 2614-2625
Author(s):  
Xin Sui ◽  
Yi-Ming Li
Keyword(s):  
Protein Localization ◽  
The Other ◽  
Related Protein ◽  
Deubiquitinating Enzymes ◽  
Post Translational Modifications ◽  
Physiological Processes ◽  
Complex Protein ◽  
Recombinant Technology ◽  
Functional Mechanisms

: Ubiquitination is one of the most extensive post-translational modifications in eukaryotes and is involved in various physiological processes such as protein degradation, autophagy, protein interaction, and protein localization. The ubiquitin (Ub)-related protein machines include Ub-activating enzymes (E1s), Ub-conjugating enzymes (E2s), Ub ligases (E3s), deubiquitinating enzymes (DUBs), p97, and the proteasomes. In recent years, the role of DUBs has been extensively studied and relatively well understood. On the other hand, the functional mechanisms of the other more complex ubiquitin-processing protein machines (e.g., E3, p97, and proteasomes) are still to be sufficiently well explored due to their intricate nature. One of the hurdles facing the studies of these complex protein machines is the challenge of developing tailor-designed structurally defined model substrates, which unfortunately cannot be directly obtained using recombinant technology. Consequently, the acquisition and synthesis of the ubiquitin tool molecules are essential for the elucidation of the functions and structures of the complex ubiquitin-processing protein machines. This paper aims to highlight recent studies on these protein machines based on the synthetic ubiquitin tool molecules.

The role of proteomics in studies of protein moonlighting

2014 ◽  
Vol 42 (6) ◽  
pp. 1698-1703 ◽  
Author(s):  
Robert J. Beynon ◽  
Dean Hammond ◽  
Victoria Harman ◽  
Yvonne Woolerton
Keyword(s):  
Post Translational Modifications ◽  
Multiple Functions ◽  
Protein Mixture ◽  
Complex Protein Mixture ◽  
Complex Protein ◽  
Quantitative Approaches

The increasing acceptance that proteins may exert multiple functions in the cell brings with it new analytical challenges that will have an impact on the field of proteomics. Many proteomics workflows begin by destroying information about the interactions between different proteins, and the reduction of a complex protein mixture to constituent peptides also scrambles information about the combinatorial potential of post-translational modifications. To bring the focus of proteomics on to the domain of protein moonlighting will require novel analytical and quantitative approaches.

scholarly journals A Role for theSaccharomyces cerevisiaeRENT Complex Protein Net1 inHMRSilencing

Genetics ◽  
2002 ◽  
Vol 161 (4) ◽  
pp. 1411-1423
Author(s):  
Daniela Kasulke ◽  
Stefanie Seitz ◽  
Ann E Ehrenhofer-Murray
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Protein A ◽  
Rdna Locus ◽  
The Other ◽  
Central Component ◽  
Yeast Saccharomyces Cerevisiae ◽  
Sir Proteins ◽  
Complex Protein ◽  
Subtelomeric Regions

AbstractSilencing in the yeast Saccharomyces cerevisiae is known in three classes of loci: in the silent mating-type loci HML and HMR, in subtelomeric regions, and in the highly repetitive rDNA locus, which resides in the nucleolus. rDNA silencing differs markedly from the other two classes of silencing in that it requires a DNA-associated protein complex termed RENT. The Net1 protein, a central component of RENT, is required for nucleolar integrity and the control of exit from mitosis. Another RENT component is the NAD+-dependent histone deacetylase Sir2, which is the only silencing factor known to be shared among the three classes of silencing. Here, we investigated the role of Net1 in HMR silencing. The mutation net1-1, as well as NET1 expression from a 2μ-plasmid, restored repression at silencing-defective HMR loci. Both effects were strictly dependent on the Sir proteins. We found overexpressed Net1 protein to be directly associated with the HMR-E silencer, suggesting that Net1 could interact with silencer binding proteins and recruit other silencing factors to the silencer. In agreement with this, Net1 provided ORC-dependent, Sir1-independent silencing when artificially tethered to the silencer. In contrast, our data suggested that net1-1 acted indirectly in HMR silencing by releasing Sir2 from the nucleolus, thus shifting the internal competition for Sir2 from the silenced loci toward HMR.

scholarly journals Turning the Knobs: The Impact of Post-translational Modifications on Carbon Metabolism

2022 ◽  
Vol 12 ◽  
Author(s):  
Cleverson C. Matiolli ◽  
Rafael Cavém Soares ◽  
Hugo L. S. Alves ◽  
Isabel A. Abreu
Keyword(s):  
Carbon Metabolism ◽  
Biotic And Abiotic Stresses ◽  
Holistic View ◽  
Post Translational Modifications ◽  
Adverse Conditions ◽  
Protein Protein Interaction ◽  
Physiological Processes ◽  
Protein Properties ◽  
The Impact

Plants rely on the carbon fixed by photosynthesis into sugars to grow and reproduce. However, plants often face non-ideal conditions caused by biotic and abiotic stresses. These constraints impose challenges to managing sugars, the most valuable plant asset. Hence, the precise management of sugars is crucial to avoid starvation under adverse conditions and sustain growth. This review explores the role of post-translational modifications (PTMs) in the modulation of carbon metabolism. PTMs consist of chemical modifications of proteins that change protein properties, including protein-protein interaction preferences, enzymatic activity, stability, and subcellular localization. We provide a holistic view of how PTMs tune resource distribution among different physiological processes to optimize plant fitness.

Placebo Analgesia Changes on Self-Pain and Empathy for Pain: Influences of Event-Related EEG Oscillations, Heart Rate Variability, and Personality

2021 ◽  
Author(s):  
Vilfredo De Pascalis ◽  
Arianna Vecchio
Keyword(s):  
Spectral Power ◽  
The Other ◽  
Behavioral Inhibition System ◽  
Placebo Analgesia ◽  
Mediating Role ◽  
Physiological Processes ◽  
Experienced Pain ◽  
Empathy For Pain ◽  
Empathic Ability

Abstract We induced placebo analgesia (PA), a phenomenon explicitly attenuating the self-pain feeling, to assess whether this resulted in reduced empathy pain when witnessing a confederate undergoing such pain experience. We recorded EEG and electrocardiogram during a painful control and PA treatment in healthy adults who rated their experienced pain and empathy for pain. We derived HRV changes and, using wavelet analysis of non-phase-locked event-related EEG oscillations, EEG spectral power differences for self-pain and other-pain conditions. First-hand PA produced a reduction of self-pain and self-unpleasantness, whereas we observed only a slight decrease of other unpleasantness. We derived linear combinations of HRV and EEG band power changes significantly associated with self-pain and empathy for pain changes using PCAs. We found that relative HR-slowing together with decreased midline ϑ-band (4-8 Hz) power directly influenced self-pain reduction and, indirectly, through chained mediating effects of the Behavioral Inhibition System and Fight-Flight-Freezing System traits. In the other-pain condition, we detected a direct influence of the midline β2-band (22-30 Hz) power reduction on the other-pain decline with a positive mediating role of Total Empathic Ability. These findings suggest that PA modulation of first-hand versus other pain relies on functionally different physiological processes involving different personality traits.

scholarly journals Molecular Mechanisms at the Basis of Plasticity in the Developing Visual Cortex: Epigenetic Processes and Gene Programs

2013 ◽  
Vol 7 ◽  
pp. JEN.S12958 ◽  
Author(s):  
José Fernando Maya-Vetencourt ◽  
Tommaso Pizzorusso
Keyword(s):  
Visual Cortex ◽  
Structural Changes ◽  
Molecular Mechanisms ◽  
Cortical Plasticity ◽  
Epigenetic Alterations ◽  
Physiological Processes ◽  
Extracellular Matrix Molecules ◽  
Visual Cortical ◽  
Functional Mechanisms

Neuronal circuitries in the mammalian visual system change as a function of experience. Sensory experience modifies neuronal networks connectivity via the activation of different physiological processes such as excitatory/inhibitory synaptic transmission, neurotrophins, and signaling of extracellular matrix molecules. Long-lasting phenomena of plasticity occur when intracellular signal transduction pathways promote epigenetic alterations of chromatin structure that regulate the induction of transcription factors that in turn drive the expression of downstream targets, the products of which then work via the activation of structural and functional mechanisms that modify synaptic connectivity. Here, we review recent findings in the field of visual cortical plasticity while focusing on how physiological mechanisms associated with experience promote structural changes that determine functional modifications of neural circuitries in V1. We revise the role of microRNAs as molecular transducers of environmental stimuli and the role of immediate early genes that control gene expression programs underlying plasticity in the developing visual cortex.

scholarly journals The Role of E3 Ubiquitin Ligases and Deubiquitinases in Inflammatory Bowel Disease: Friend or Foe?

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Zou ◽  
Qi-Shan Zeng ◽  
Jiao Nie ◽  
Jia-Hui Yang ◽  
Zhen-Yi Luo ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Cell Cycle Progression ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Immune Disorder ◽  
Post Translational Modifications ◽  
Physiological Processes ◽  
Inflammatory Bowel

Inflammatory bowel disease (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), exhibits a complex multifactorial pathogenesis involving genetic susceptibility, imbalance of gut microbiota, mucosal immune disorder and environmental factors. Recent studies reported associations between ubiquitination and deubiquitination and the occurrence and development of inflammatory bowel disease. Ubiquitination modification, one of the most important types of post-translational modifications, is a multi-step enzymatic process involved in the regulation of various physiological processes of cells, including cell cycle progression, cell differentiation, apoptosis, and innate and adaptive immune responses. Alterations in ubiquitination and deubiquitination can lead to various diseases, including IBD. Here, we review the role of E3 ubiquitin ligases and deubiquitinases (DUBs) and their mediated ubiquitination and deubiquitination modifications in the pathogenesis of IBD. We highlight the importance of this type of posttranslational modification in the development of inflammation, and provide guidance for the future development of targeted therapeutics in IBD.

Homeostatic Role of Autophagy in Hepatocytes

2018 ◽  
Vol 38 (04) ◽  
pp. 308-319 ◽  
Author(s):  
Bilon Khambu ◽  
Shengmin Yan ◽  
Nazmul Huda ◽  
Gang Liu ◽  
Xiao-Ming Yin
Keyword(s):  
Direct Effect ◽  
Liver Diseases ◽  
Metabolic Regulation ◽  
Molecular Mechanisms ◽  
Nutrient Supply ◽  
The Other ◽  
Chronic Liver Diseases ◽  
Physiological Processes ◽  
Abnormal Accumulation

AbstractAutophagy actively participates in the physiological process of the liver. While the direct effect of autophagy may be limited to the sequestration and degradation of a selective cargo, its overall impact can be broad, affecting many more physiological processes regulated by the particular cargo. This review will discuss two aspects of the importance of autophagy in the liver: metabolic regulation in response to feeding and starvation, and pathological consequences in the absence of autophagy. These two aspects illustrate the homeostatic functions of autophagy in the liver, one in a more direct fashion, regulating the cellular nutrient supply, and the other in a more indirect fashion, controlling the pathological signaling triggered by the abnormal accumulation of cargos. Remarkably, the hepatic pathology in autophagy-deficient livers does not seem different from that presented in other chronic liver diseases. Autophagy deficiency can be a model for the study of the relevant molecular mechanisms.

scholarly journals Tubulin in Platelets: When the Shape Matters

2019 ◽  
Vol 20 (14) ◽  
pp. 3484 ◽  
Author(s):  
Ernesto José Cuenca-Zamora ◽  
Francisca Ferrer-Marín ◽  
José Rivera ◽  
Raúl Teruel-Montoya
Keyword(s):  
Gene Encoding ◽  
Vascular Integrity ◽  
Post Translational Modifications ◽  
Molecular Alterations ◽  
Physiological Processes ◽  
Short Lifespan ◽  
Platelet Morphology ◽  
Cytoskeleton Reorganization ◽  
High Production

Platelets are anuclear cells with a short lifespan that play an essential role in many pathophysiological processes, including haemostasis, inflammation, infection, vascular integrity, and metastasis. Billions of platelets are produced daily from megakaryocytes (platelet precursors). Despite this high production, the number of circulating platelets is stable and, under resting conditions, they maintain their typical discoid shape thanks to cytoskeleton proteins. The activation of platelets is associated with dynamic and rapid changes in the cytoskeleton. Two cytoskeletal polymer systems exist in megakaryocytes and platelets: actin filaments and microtubules, based on actin, and α- and β-tubulin heterodimers, respectively. Herein, we will focus on platelet-specific tubulins and their alterations and role of the microtubules skeleton in platelet formation (thrombopoiesis). During this process, microtubules mediate elongation of the megakaryocyte extensions (proplatelet) and granule trafficking from megakaryocytes to nascent platelets. In platelets, microtubules form a subcortical ring, the so-called marginal band, which confers the typical platelet discoid shape and is also responsible for changes in platelet morphology upon activation. Molecular alterations in the gene encoding β1 tubulin and microtubules post-translational modifications may result in quantitative or qualitative changes in tubulin, leading to altered cytoskeleton reorganization that may induce changes in the platelet number (thrombocytopenia), morphology or function. Consequently, β1-tubulin modifications may participate in pathological and physiological processes, such as development.

scholarly journals Reversible Dimerization of Human Serum Albumin

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 108
Author(s):  
Alexey Chubarov ◽  
Anna Spitsyna ◽  
Olesya Krumkacheva ◽  
Dmitry Mitin ◽  
Daniil Suvorov ◽  
...  
Keyword(s):  
Human Serum Albumin ◽  
Serum Albumin ◽  
Human Serum ◽  
Spin Labels ◽  
Dimer Formation ◽  
Paramagnetic Resonance ◽  
Post Translational Modifications ◽  
Physiological Processes ◽  
Reversible Dimerization

Pulsed Dipolar Spectroscopy (PDS) methods of Electron Paramagnetic Resonance (EPR) were used to detect and characterize reversible non-covalent dimers of Human Serum Albumin (HSA), the most abundant protein in human plasma. The spin labels, MTSL and OX063, were attached to Cys-34 and these chemical modifications of Cys-34 did affect the dimerization of HSA, indicating that other post-translational modifications can modulate dimer formation. At physiologically relevant concentrations, HSA does form weak, non-covalent dimers with a well-defined structure. Dimer formation is readily reversible into monomers. Dimerization is very relevant to the role of HSA in the transport, binding, and other physiological processes.

Plasma Levels of Protein S, Protein C, and Factor X: Effects of Sex, Hormonal State and Age

1995 ◽  
Vol 74 (05) ◽  
pp. 1271-1275 ◽  
Author(s):  
C M A Henkens ◽  
V J J Bom ◽  
W van der Schaaf ◽  
P M Pelsma ◽  
C Th Smit Sibinga ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Postmenopausal Women ◽  
Protein C ◽  
Blood Donors ◽  
Premenopausal Women ◽  
Protein S ◽  
The Other ◽  
Factor X ◽  
Normal Ranges

SummaryWe measured total and free protein S (PS), protein C (PC) and factor X (FX) in 393 healthy blood donors to assess differences in relation to sex, hormonal state and age. All measured proteins were lower in women as compared to men, as were levels in premenopausal women as compared to postmenopausal women. Multiple regression analysis showed that both age and subgroup (men, pre- and postmenopausal women) were of significance for the levels of total and free PS and PC, the subgroup effect being caused by the differences between the premenopausal women and the other groups. This indicates a role of sex-hormones, most likely estrogens, in the regulation of levels of pro- and anticoagulant factors under physiologic conditions. These differences should be taken into account in daily clinical practice and may necessitate different normal ranges for men, pre- and postmenopausal women.

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