scholarly journals The Role of Primary Cilia in the Crosstalk between the Ubiquitin–Proteasome System and Autophagy

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 241 ◽  
Author(s):  
Antonia Wiegering ◽  
Ulrich Rüther ◽  
Christoph Gerhardt
Keyword(s):  
Protein Degradation ◽  
Primary Cilia ◽  
Current Knowledge ◽  
Ubiquitin Proteasome System ◽  
Review Article ◽  
The Other ◽  
Novel Studies ◽  
Safety Mechanism ◽  
Ubiquitin Proteasome

Protein degradation is a pivotal process for eukaryotic development and homeostasis. The majority of proteins are degraded by the ubiquitin–proteasome system and by autophagy. Recent studies describe a crosstalk between these two main eukaryotic degradation systems which allows for establishing a kind of safety mechanism. If one of these degradation systems is hampered, the other compensates for this defect. The mechanism behind this crosstalk is poorly understood. Novel studies suggest that primary cilia, little cellular protrusions, are involved in the regulation of the crosstalk between the two degradation systems. In this review article, we summarise the current knowledge about the association between cilia, the ubiquitin–proteasome system and autophagy.

scholarly journals Intracellular Dynamics of the Ubiquitin-Proteasome-System

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 367 ◽  
Author(s):  
Maisha Chowdhury ◽  
Cordula Enenkel
Keyword(s):  
Cell Cycle ◽  
Protein Degradation ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Ubiquitin Proteasome System ◽  
Yeast Cells ◽  
Ubiquitin Chain ◽  
Dividing Cells ◽  
Ubiquitin Proteasome

The ubiquitin-proteasome system is the major degradation pathway for short-lived proteins in eukaryotic cells. Targets of the ubiquitin-proteasome-system are proteins regulating a broad range of cellular processes including cell cycle progression, gene expression, the quality control of proteostasis and the response to geno- and proteotoxic stress. Prior to degradation, the proteasomal substrate is marked with a poly-ubiquitin chain. The key protease of the ubiquitin system is the proteasome. In dividing cells, proteasomes exist as holo-enzymes composed of regulatory and core particles. The regulatory complex confers ubiquitin-recognition and ATP dependence on proteasomal protein degradation. The catalytic sites are located in the proteasome core particle. Proteasome holo-enzymes are predominantly nuclear suggesting a major requirement for proteasomal proteolysis in the nucleus. In cell cycle arrested mammalian or quiescent yeast cells, proteasomes deplete from the nucleus and accumulate in granules at the nuclear envelope (NE) / endoplasmic reticulum ( ER) membranes. In prolonged quiescence, proteasome granules drop off the nuclear envelopeNE / ER membranes and migrate as droplet-like entitiesstable organelles  throughout the cytoplasm, as thoroughly investigated in yeast. When quiescence yeast cells are allowed to resume growth, proteasome granules clear and proteasomes are rapidly imported into the nucleus.Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm.Most of our current knowledge is based on studies in yeast. Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells, which comprise the majority of our body’s cells.

scholarly journals The Role of ATG16 in Autophagy and The Ubiquitin Proteasome System

Cells ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 2 ◽  
Author(s):  
Qiuhong Xiong ◽  
Wenjing Li ◽  
Ping Li ◽  
Min Yang ◽  
Changxin Wu ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Current Knowledge ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathways ◽  
Autophagosome Formation ◽  
Cell Homeostasis ◽  
Independent Functions ◽  
Ubiquitin Proteasome

Autophagy and the ubiquitin proteasome system (UPS) are the two major cellular degradation pathways, which are critical for the maintenance of cell homeostasis. The two pathways differ in their mechanisms and clients. The evolutionary conserved ATG16 plays a key role in autophagy and appears to link autophagy with the UPS. Here, we review the role of ATG16 in different species. We summarize the current knowledge of its functions in autophagosome membrane expansion and autophagosome formation, in Crohn’s disease, and in bacterial sequestration. In addition, we provide information on its autophagy-independent functions and its role in the crosstalk between autophagy and the UPS.

scholarly journals Canonical and non-canonical autophagy pathways in microglia

2020 ◽  
Author(s):  
Julia Jülg ◽  
Laura Strohm ◽  
Christian Behrends
Keyword(s):  
Neurodegenerative Disorders ◽  
Current Knowledge ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Brain Health ◽  
The Past ◽  
Long Time ◽  
Ubiquitin Proteasome ◽  
Autophagy Activity

Besides the ubiquitin-proteasome-system, autophagy is a major degradation pathway within cells. It delivers invading pathogens, damaged organelles, aggregated proteins and other macromolecules from the cytosol to the lysosome for bulk degradation. This so-called canonical autophagy activity contributes to the maintenance of organelle, protein and metabolite homeostasis as well as innate immunity. Over the past years, numerous studies rapidly deepened our knowledge on the autophagy machinery and its regulation; driven by the fact that impairment of autophagy is associated with several human pathologies including cancer, immune diseases and neurodegenerative disorders. Unexpectedly, components of the autophagic machinery were also found to participate in various processes that did not involve lysosomal delivery of cytosolic constituents. These functions are hereafter defined as non-canonical autophagy. Regarding neurodegenerative diseases, most research was performed in neurons, while for a long-time microglia received considerably less attention. Concomitant with the notion that microglia greatly contribute to brain health, the understanding of the role of autophagy in microglia expanded. To facilitate an overview of the current knowledge, we present herein the fundamentals as well as the recent advances of canonical and non-canonical autophagy functions in microglia.

scholarly journals The ubiquitin–proteasome system in regulation of the skeletal muscle homeostasis and atrophy: from basic science to disorders

2020 ◽  
Vol 70 (1) ◽  
Author(s):  
Yasuo Kitajima ◽  
Kiyoshi Yoshioka ◽  
Naoki Suzuki
Keyword(s):  
Skeletal Muscle ◽  
Protein Degradation ◽  
Ubiquitin Proteasome System ◽  
Intracellular Protein ◽  
Muscle Stem Cells ◽  
Muscle Diseases ◽  
Intracellular Protein Degradation ◽  
Ubiquitin Proteasome ◽  
Muscle Homeostasis

Abstract Skeletal muscle is one of the most abundant and highly plastic tissues. The ubiquitin–proteasome system (UPS) is recognised as a major intracellular protein degradation system, and its function is important for muscle homeostasis and health. Although UPS plays an essential role in protein degradation during muscle atrophy, leading to the loss of muscle mass and strength, its deficit negatively impacts muscle homeostasis and leads to the occurrence of several pathological phenotypes. A growing number of studies have linked UPS impairment not only to matured muscle fibre degeneration and weakness, but also to muscle stem cells and deficiency in regeneration. Emerging evidence suggests possible links between abnormal UPS regulation and several types of muscle diseases. Therefore, understanding of the role of UPS in skeletal muscle may provide novel therapeutic insights to counteract muscle wasting, and various muscle diseases. In this review, we focussed on the role of proteasomes in skeletal muscle and its regeneration, including a brief explanation of the structure of proteasomes. In addition, we summarised the recent findings on several diseases and elaborated on how the UPS is related to their pathological states.

scholarly journals Doxorubicin and NRG-1/erbB4-Deficiency Affect Gene Expression Profile: Involving Protein Homeostasis in Mouse

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Cecilia Vasti ◽  
Henning Witt ◽  
Matilde Said ◽  
Patricia Sorroche ◽  
Hernán García-Rivello ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Ventricular Remodeling ◽  
Current Knowledge ◽  
Ubiquitin Proteasome System ◽  
Neuregulin 1 ◽  
Hypertrophic Response ◽  
Ubiquitin Proteasome

The accumulating evidence demonstrates the essential role of neuregulin-1 signaling in the adult heart, and, moreover, indicates that an impaired neuregulin signaling exacerbates the doxorubicin-mediated cardiac toxicity. Despite this strong data, the specific cardiomyocyte targets of the active erbB2/erbB4 heterodimer remain unknown. In this paper, we examined pathways involved in cardiomyocyte damage as a result of the cardiac sensitization to anthracycline toxicity in the ventricular muscle-specific erbB4 knockout mouse. We performed morphological analyses to evaluate the ventricular remodeling and employed a cDNA microarray to assess the characteristic gene expression profile, verified data by real-time RT-PCR, and then grouped into functional categories and pathways. We confirm the upregulation of genes related to the classical signature of a hypertrophic response, implicating an erbB2-dependent mechanism in doxorubicin-treated erbB4-KO hearts. Our results indicate the remarkable downregulation of IGF-I/PI-3′ kinase pathway and extends our current knowledge by uncovering an altered ubiquitin-proteasome system leading to cardiomyocyte autophagic vacuolization.

scholarly journals Chronic contractile activity upregulates the proteasome system in rabbit skeletal muscle

2000 ◽  
Vol 88 (3) ◽  
pp. 1134-1141 ◽  
Author(s):  
George A. Ordway ◽  
P. Darrell Neufer ◽  
Eva R. Chin ◽  
George N. DeMartino
Keyword(s):  
Skeletal Muscle ◽  
Protein Degradation ◽  
Contractile Activity ◽  
Motor Nerve ◽  
Ubiquitin Proteasome System ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Hydrolysis Of

Remodeling of skeletal muscle in response to altered patterns of contractile activity is achieved, in part, by the regulated degradation of cellular proteins. The ubiquitin-proteasome system is a dominant pathway for protein degradation in eukaryotic cells. To test the role of this pathway in contraction-induced remodeling of skeletal muscle, we used a well-established model of continuous motor nerve stimulation to activate tibialis anterior (TA) muscles of New Zealand White rabbits for periods up to 28 days. Western blot analysis revealed marked and coordinated increases in protein levels of the 20S proteasome and two of its regulatory proteins, PA700 and PA28. mRNA of a representative proteasome subunit also increased coordinately in contracting muscles. Chronic contractile activity of TA also increased total proteasome activity in extracts, as measured by the hydrolysis of a proteasome-specific peptide substrate, and the total capacity of the ubiquitin-proteasome pathway, as measured by the ATP-dependent hydrolysis of an exogenous protein substrate. These results support the potential role of the ubiquitin-proteasome pathway of protein degradation in the contraction-induced remodeling of skeletal muscle.

scholarly journals Ubiquitin–proteasome system and the role of its inhibitors in cancer therapy

Open Biology ◽  
2021 ◽  
Vol 11 (4) ◽  
Author(s):  
Fatemeh Aliabadi ◽  
Beheshteh Sohrabi ◽  
Ebrahim Mostafavi ◽  
Hamidreza Pazoki-Toroudi ◽  
Thomas J. Webster
Keyword(s):  
Cancer Therapy ◽  
Ubiquitin Proteasome System ◽  
Tumour Suppressor ◽  
The Other ◽  
Cancer Development ◽  
Chemotherapy Drugs ◽  
Advantages And Disadvantages ◽  
Fundamental Understanding ◽  
Ubiquitin Proteasome

Despite all the other cells that have the potential to prevent cancer development and metastasis through tumour suppressor proteins, cancer cells can upregulate the ubiquitin–proteasome system (UPS) by which they can degrade tumour suppressor proteins and avoid apoptosis. This system plays an extensive role in cell regulation organized in two steps. Each step has an important role in controlling cancer. This demonstrates the importance of understanding UPS inhibitors and improving these inhibitors to foster a new hope in cancer therapy. UPS inhibitors, as less invasive chemotherapy drugs, are increasingly used to alleviate symptoms of various cancers in malignant states. Despite their success in reducing the development of cancer with the lowest side effects, thus far, an appropriate inhibitor that can effectively inactivate this system with the least drug resistance has not yet been fully investigated. A fundamental understanding of the system is necessary to fully elucidate its role in causing/controlling cancer. In this review, we first comprehensively investigate this system, and then each step containing ubiquitination and protein degradation as well as their inhibitors are discussed. Ultimately, its advantages and disadvantages and some perspectives for improving the efficiency of these inhibitors are discussed.

scholarly journals Intracellular Dynamics of the Ubiquitin-Proteasome-System

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 367 ◽  
Author(s):  
Maisha Chowdhury ◽  
Cordula Enenkel
Keyword(s):  
Cell Cycle ◽  
Protein Degradation ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Ubiquitin Proteasome System ◽  
Yeast Cells ◽  
Ubiquitin Chain ◽  
Dividing Cells ◽  
Ubiquitin Proteasome

The ubiquitin-proteasome system is the major degradation pathway for short-lived proteins in eukaryotic cells. Targets of the ubiquitin-proteasome-system are proteins regulating a broad range of cellular processes including cell cycle progression, gene expression, the quality control of proteostasis and the response to geno- and proteotoxic stress. Prior to degradation, the proteasomal substrate is marked with a poly-ubiquitin chain. The key protease of the ubiquitin system is the proteasome. In dividing cells, proteasomes exist as holo-enzymes composed of regulatory and core particles. The regulatory complex confers ubiquitin-recognition and ATP dependence on proteasomal protein degradation. The catalytic sites are located in the proteasome core particle. Proteasome holo-enzymes are predominantly nuclear suggesting a major requirement for proteasomal proteolysis in the nucleus. In cell cycle arrested mammalian or quiescent yeast cells, proteasomes deplete from the nucleus and accumulate in granules at the nuclear envelope (NE) / endoplasmic reticulum (ER) membranes. In prolonged quiescence, proteasome granules drop off the NE / ER membranes and migrate as stable organelles throughout the cytoplasm, as thoroughly investigated in yeast. When quiescence yeast cells are allowed to resume growth, proteasome granules clear and proteasomes are rapidly imported into the nucleus.Here, we summarize our knowledge about the enigmatic structure of proteasome storage granules and the trafficking of proteasomes and their substrates between the cyto- and nucleoplasm.Most of our current knowledge is based on studies in yeast. Their translation to mammalian cells promises to provide keen insight into protein degradation in non-dividing cells which comprise the majority of our body’s cells.

The Ubiquitin-Proteasome System and Memory: Moving Beyond Protein Degradation

2018 ◽  
Vol 24 (6) ◽  
pp. 639-651 ◽  
Author(s):  
Timothy J. Jarome ◽  
Rishi K. Devulapalli
Keyword(s):  
Protein Degradation ◽  
Chromatin Remodeling ◽  
Ubiquitin Proteasome System ◽  
Degradation Pathway ◽  
Memory Formation ◽  
Consolidation Process ◽  
Future Studies ◽  
Cellular Models ◽  
Ubiquitin Proteasome

Cellular models of memory formation have focused on the need for protein synthesis. Recently, evidence has emerged that protein degradation mediated by the ubiquitin-proteasome system (UPS) is also important for this process. This has led to revised cellular models of memory formation that focus on a balance between protein degradation and synthesis. However, protein degradation is only one function of the UPS. Studies using single-celled organisms have shown that non-proteolytic ubiquitin-proteasome signaling is involved in histone modifications and DNA methylation, suggesting that ubiquitin and the proteasome can regulate chromatin remodeling independent of protein degradation. Despite this evidence, the idea that the UPS is more than a protein degradation pathway has not been examined in the context of memory formation. In this article, we summarize recent findings implicating protein degradation in memory formation and discuss various ways in which both ubiquitin signaling and the proteasome could act independently to regulate epigenetic-mediated transcriptional processes necessary for learning-dependent synaptic plasticity. We conclude by proposing comprehensive models of how non-proteolytic functions of the UPS could work in concert to control epigenetic regulation of the cellular memory consolidation process, which will serve as a framework for future studies examining the role of the UPS in memory formation.

scholarly journals Endoplasmic reticulum stress and the protein degradation system in ophthalmic diseases

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8638 ◽  
Author(s):  
Jing-Yao Song ◽  
Xue-Guang Wang ◽  
Zi-Yuan Zhang ◽  
Lin Che ◽  
Bin Fan ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Er Stress ◽  
Protein Degradation ◽  
Ubiquitin Proteasome System ◽  
Ubiquitin Proteasome ◽  
Ophthalmic Diseases ◽  
Stress Damage ◽  
Er Homeostasis

Objective Endoplasmic reticulum (ER) stress is involved in the pathogenesis of various ophthalmic diseases, and ER stress-mediated degradation systems play an important role in maintaining ER homeostasis during ER stress. The purpose of this review is to explore the potential relationship between them and to find their equilibrium sites. Design This review illustrates the important role of reasonable regulation of the protein degradation system in ER stress-mediated ophthalmic diseases. There were 128 articles chosen for review in this study, and the keywords used for article research are ER stress, autophagy, UPS, ophthalmic disease, and ocular. Data sources The data are from Web of Science, PubMed, with no language restrictions from inception until 2019 Jul. Results The ubiquitin proteasome system (UPS) and autophagy are important degradation systems in ER stress. They can restore ER homeostasis, but if ER stress cannot be relieved in time, cell death may occur. However, they are not independent of each other, and the relationship between them is complementary. Therefore, we propose that ER stability can be achieved by adjusting the balance between them. Conclusion The degradation system of ER stress, UPS and autophagy are interrelated. Because an imbalance between the UPS and autophagy can cause cell death, regulating that balance may suppress ER stress and protect cells against pathological stress damage.

Sign in / Sign up

Export Citation Format

Share Document