scholarly journals A comprehensive framework of E2–RING E3 interactions of the human ubiquitin–proteasome system

2009 ◽  
Vol 5 (1) ◽  
pp. 317 ◽  
Author(s):  
Sjoerd J L van Wijk ◽  
Sjoerd J de Vries ◽  
Patrick Kemmeren ◽  
Anding Huang ◽  
Rolf Boelens ◽  
...  
Keyword(s):  
Ubiquitin Proteasome System ◽  
Human Ubiquitin ◽  
Ubiquitin Proteasome ◽  
Comprehensive Framework ◽  
Ring E3

scholarly journals A comprehensive framework of E2–RING E3 interactions of the human ubiquitin–proteasome system

2009 ◽  
Vol 5 (1) ◽  
pp. 295 ◽  
Author(s):  
Sjoerd J L van Wijk ◽  
Sjoerd J de Vries ◽  
Patrick Kemmeren ◽  
Anding Huang ◽  
Rolf Boelens ◽  
...  
Keyword(s):  
Ubiquitin Proteasome System ◽  
Human Ubiquitin ◽  
Ubiquitin Proteasome ◽  
Comprehensive Framework ◽  
Ring E3

scholarly journals Keratin 6a reorganization for ubiquitin–proteasomal processing is a direct antimicrobial response

2017 ◽  
Vol 217 (2) ◽  
pp. 731-744 ◽  
Author(s):  
Jonathan K.L. Chan ◽  
Don Yuen ◽  
Priscilla Hiu-Mei Too ◽  
Yan Sun ◽  
Belinda Willard ◽  
...  
Keyword(s):  
Ubiquitin Proteasome System ◽  
Immune Defense ◽  
Antigenic Peptides ◽  
Corneal Epithelial ◽  
E3 Ligases ◽  
Appreciable Increase ◽  
Host Defense Response ◽  
Ubiquitin Proteasome ◽  
Ring E3 Ligases ◽  
Ring E3

Skin and mucosal epithelia deploy antimicrobial peptides (AMPs) to eliminate harmful microbes. We reported that the intermediate filament keratin 6a (K6a) is constitutively processed into antimicrobial fragments in corneal epithelial cells. In this study, we show that K6a network remodeling is a host defense response that directly up-regulates production of keratin-derived AMPs (KAMPs) by the ubiquitin–proteasome system (UPS). Bacterial ligands trigger K6a phosphorylation at S19, S22, S37, and S60, leading to network disassembly. Mutagenic analysis of K6a confirmed that the site-specific phosphorylation augmented its solubility. K6a in the cytosol is ubiquitinated by cullin-RING E3 ligases for subsequent proteasomal processing. Without an appreciable increase in K6a gene expression and proteasome activity, a higher level of cytosolic K6a results in enhanced KAMP production. Although proteasome-mediated proteolysis is known to produce antigenic peptides in adaptive immunity, our findings demonstrate its new role in producing AMPs for innate immune defense. Manipulating K6a phosphorylation or UPS activity may provide opportunities to harness the innate immunity of epithelia against infection.

scholarly journals Effect of Drosophila ubiquitin carboxylterminal hydrolase overexpression on the Drosophila melanogaster eye development

2019 ◽  
Vol 2 (4) ◽  
pp. 40-46
Author(s):  
Trang Thi Thuy Cao ◽  
Thao Thi Phuong Dang
Keyword(s):  
Drosophila Melanogaster ◽  
Eye Development ◽  
Ubiquitin Proteasome System ◽  
Pigment Cells ◽  
Deubiquitinating Enzyme ◽  
Human Ubiquitin ◽  
Ubiquitin Proteasome ◽  
Specific Proteins

Human ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1) is a member of deubiquitinating enzyme group and a component of ubiquitin-proteasome system. Being one of the neuron-specific proteins, abnormalities of UCH-L1 was observed in several neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease. On the other hand, UCH-L1 was also found to be present in various kinds of cancers with inconsistent acting reported in different studies. Together these records indicated the involvement of UCH-L1 in maintaining normal activities of cells, tissues and organs. However, in vivo significance of the protein remains unclear. In addition, among the attempts made to approach the biological function of UCHL1, there has been no previous report addressing its part in development. In order to explore the function of UCH-L1, we utilized Drosophila melanogaster as model to investigate effects of dUCH (a Drosophila homologue of human UCH-L1) on the development. Particularly in Drosophila eye development, in this study. Our experimental results revealed that specific overexpression of dUCH in eye tissue induced the disruption in ommatidia orientation and defects in differentiation of pigment cells. These results are evidence that support the role of dUCH as a development mediating factor.

The ubiquitin–proteasome system and skeletal muscle wasting

2005 ◽  
Vol 41 ◽  
pp. 173-186 ◽  
Author(s):  
Didier Attaix ◽  
Sophie Ventadour ◽  
Audrey Codran ◽  
Daniel Béchet ◽  
Daniel Taillandier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Proteolytic Enzymes ◽  
Cathepsin L ◽  
Ubiquitin Proteasome System ◽  
Complete Breakdown ◽  
Skeletal Muscle Proteins ◽  
Ubiquitin Proteasome ◽  
Tripeptidyl Peptidase Ii ◽  
F Box Protein

The ubiquitin–proteasome system (UPS) is believed to degrade the major contractile skeletal muscle proteins and plays a major role in muscle wasting. Different and multiple events in the ubiquitination, deubiquitination and proteolytic machineries are responsible for the activation of the system and subsequent muscle wasting. However, other proteolytic enzymes act upstream (possibly m-calpain, cathepsin L, and/or caspase 3) and downstream (tripeptidyl-peptidase II and aminopeptidases) of the UPS, for the complete breakdown of the myofibrillar proteins into free amino acids. Recent studies have identified a few critical proteins that seem necessary for muscle wasting {i.e. the MAFbx (muscle atrophy F-box protein, also called atrogin-1) and MuRF-1 [muscle-specific RING (really interesting new gene) finger 1] ubiquitin–protein ligases}. The characterization of their signalling pathways is leading to new pharmacological approaches that can be useful to block or partially prevent muscle wasting in human patients.

The ubiquitin–proteasome system and skeletal muscle wasting

2005 ◽  
Vol 41 (1) ◽  
pp. 173 ◽  
Author(s):  
Didier Attaix ◽  
Sophie Ventadour ◽  
Audrey Codran ◽  
Daniel Béchet ◽  
Daniel Taillandier ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Wasting ◽  
Ubiquitin Proteasome System ◽  
Skeletal Muscle Wasting ◽  
Ubiquitin Proteasome

Theoretical Studies of the Acid-Base Equilibria in a Model Active Site of the Human 20S Proteasome

2020 ◽  
Author(s):  
Jon Uranga ◽  
Lukas Hasecke ◽  
Jonny Proppe ◽  
Jan Fingerhut ◽  
Ricardo A. Mata
Keyword(s):  
Active Site ◽  
Boronic Acid ◽  
Computational Study ◽  
Ubiquitin Proteasome System ◽  
Bayesian Optimization ◽  
Inhibition Mechanism ◽  
20S Proteasome ◽  
Acid Base ◽  
Ubiquitin Proteasome ◽  
Infection Cycles

The 20S Proteasome is a macromolecule responsible for the chemical step in the ubiquitin-proteasome system of degrading unnecessary and unused proteins of the cell. It plays a central role both in the rapid growth of cancer cells as well as in viral infection cycles. Herein, we present a computational study of the acid-base equilibria in an active site of the human proteasome, an aspect which is often neglected despite the crucial role protons play in the catalysis. As example substrates, we take the inhibition by epoxy and boronic acid containing warheads. We have combined cluster quantum mechanical calculations, replica exchange molecular dynamics and Bayesian optimization of non-bonded potential terms in the inhibitors. In relation to the latter, we propose an easily scalable approach to the reevaluation of non-bonded potentials making use of QM/MM dynamics information. Our results show that coupled acid-base equilibria need to be considered when modeling the inhibition mechanism. The coupling between a neighboring lysine and the reacting threonine is not affected by the presence of the inhibitor.

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