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20S proteasome

Marzena Tylicka, Ewa Matuszczak, Maria Karpińska, Adam Hermanowicz, Wojciech Dębek, Halina Ostrowska
Operations of varying duration cause the release of a number of inflammatory mediators, in particular cytokines which lead to proteasome and acute-phase reactions. The purpose of this novel human study, was to characterize inflammatory response in children undergoing laparoscopic cholecystectomy, by analyzing changes in selected inflammatory mediators: C-reactive protein concentration and circulating 20S proteasome activity following surgical injury and to correlate them with the duration of the surgical procedure...
October 12, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
Lisa Zondler, Marcus Kostka, Patrick Garidel, Udo Heinzelmann, Bastian Hengerer, Benjamin Mayer, Jochen H Weishaupt, Frank Gillardon, Karin M Danzer
Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide and characterized by the loss of dopaminergic neurons in the patients' midbrains. Both the presence of the protein α-synuclein in intracellular protein aggregates in surviving neurons and the genetic linking of the α-synuclein encoding gene point towards a major role of α-synuclein in PD etiology. The exact pathogenic mechanisms of PD development are not entirely described to date, neither is the specific role of α-synuclein in this context...
2017: PloS One
E Matuszczak, A Sankiewicz, W Debek, E Gorodkiewicz, R Milewski, A Hermanowicz
The aim of this study was to determinate the immunoproteasome concentration in the blood plasma of children with appendicitis, and its correlation with circulating proteasome and ubiquitin carboxyl-terminal hydrolase L1 (UCHL1). Twenty-seven children with acute appendicitis, managed at the Paediatric Surgery Department, were included randomly into the study (age 2 years 9 months up to 14 years, mean age 9·5 ± 1 years). There were 10 girls and 17 boys; 18 healthy, age-matched subjects, admitted for planned surgeries served as controls...
September 23, 2017: Clinical and Experimental Immunology
Yang Wang, Qi Ding, Tao Xu, Chang-Yao Li, Dan-Dan Zhou, Lei Zhang
Manipulating the posttranslational modulator of p53 is central in the regulation of its activity and function. ISGylated p53 can be degraded by the 20S proteasome. During this process, HERC5/Ceb1, an IFN-induced HECT-type E3 ligase, mediated p53 ISGylation. In this study, we indicated that HERC5 was over-expressed in both HCC tissue samples and cell lines. Knockdown of HERC5 significantly induced the expression of p53, p21 and Bax/Bcl-2 in HCC cells, resulting in apoptosis augment. Whereas, opposite results were obtained by using HERC5 over-expression...
November 1, 2017: Toxicology and Applied Pharmacology
Enyara R Morais, Katia C Oliveira, Renato G de Paula, Alice M M Ornelas, Érika B C Moreira, Fernanda Rafacho Badoco, Lizandra G Magalhães, Sergio Verjovski-Almeida, Vanderlei Rodrigues
Proteasome is a proteolytic complex responsible for intracellular protein turnover in eukaryotes, archaea and in some actinobacteria species. Previous work has demonstrated that in Schistosoma mansoni parasites, the proteasome inhibitor MG-132 affects parasite development. However, the molecular targets affected by MG-132 in S. mansoni are not entirely known. Here, we used expression microarrays to measure the genome-wide changes in gene expression of S. mansoni adult worms exposed in vitro to MG-132, followed by in silico functional analyses of the affected genes using Ingenuity Pathway Analysis (IPA)...
2017: PloS One
Brian B Hasinoff, Daywin Patel
The alcohol abuse drug disulfiram has also been shown to exhibit potent cell growth inhibitory and anticancer activity. While a number of cellular and animal studies have suggested that disulfiram exhibits its anticancer activity through interaction with the proteasome, direct evidence for inhibition of proteasome activity is lacking. In this study we show that disulfiram potently inhibits the chymotrypsin-like activity of purified human 20S proteasome at low micromolar pharmacological concentrations. The enzyme progress curves displayed characteristics of a slow-binding reaction, similar to that observed for the FDA-approved proteasomal-targeted anticancer drugs bortezomib and carfilzomib...
September 5, 2017: Archives of Biochemistry and Biophysics
Xin Chen, Xiaolan Zhang, Jinghong Chen, Qianqian Yang, Li Yang, Dacai Xu, Peiquan Zhang, Xuejun Wang, Jinbao Liu
The ubiquitin-proteasome system (UPS) plays a central role in the regulation of proteins that control cell growth and apoptosis and has therefore become an important target for anticancer therapy. Several constitutive subunits of the 19S proteasome display deubiquitinase (DUB) activity, suggesting that ubiquitin modification of proteins is dynamically regulated. Our study and others have shown that metal complexes, such as copper complexes, can induce cancer cell apoptosis through inhibiting 19S proteasome-associated DUBs and/or 20S proteasome activity...
September 5, 2017: European Journal of Pharmacology
Hilla Solomon, Bastian Bräuning, Irit Fainer, Gili Ben-Nissan, Stav Rabani, Naomi Goldfinger, Oren Moscovitz, Zippora Shakked, Varda Rotter, Michal Sharon
The tumor suppressor p53 is a transcription factor that regulates the expression of a range of target genes in response to cellular stress. Adding to the complexity of understanding its cellular function is that in addition to the full-length protein, several p53 isoforms are produced in humans, harboring diverse expression patterns and functionalities. One isoform, Δ40p53, which lacks the first transactivation domain including the binding region for the negative regulator MDM2, was shown to be a product of alternative translation initiation...
September 8, 2017: Cell Death and Differentiation
David Ross, David Siegel
NQO1 is one of the two major quinone reductases in mammalian systems. It is highly inducible and plays multiple roles in cellular adaptation to stress. A prevalent polymorphic form of NQO1 results in an absence of NQO1 protein and activity so it is important to elucidate the specific cellular functions of NQO1. Established roles of NQO1 include its ability to prevent certain quinones from one electron redox cycling but its role in quinone detoxification is dependent on the redox stability of the hydroquinone generated by two-electron reduction...
2017: Frontiers in Physiology
Eva M Huber, Michael Groll
The heptameric proteasome activator (PA) 28αβ is known to modulate class I antigen processing by docking onto 20S proteasome core particles (CPs). The exact stoichiometry and arrangement of its α and β subunits, however, is still controversial. Here we analyzed murine PA28 complexes regarding structure and assembly. Strikingly, PA28α, PA28β, and PA28αβ preparations form heptamers, but solely PA28α and PA28αβ associate with CPs. Co-expression of α and β yields one unique PA28αβ species with an unchangeable subunit composition...
August 22, 2017: Structure
Chengrun Wang, Hong Rong, Haitao Liu, Xiaofei Wang, Yixin Gao, Ruhua Deng, Ruiyu Liu, Yun Liu, Di Zhang
The widespread application of antibiotics poses health risks for agro-ecosystems. This study examined the effects of ciproflaxin (CIP)-polluted soils (0-51.2mgCIP/kg) on the earthworm Eisenia foetida. The enhanced activities and isozyme levels of superoxide dismutase (SOD) and ascorbate peroxidase after 15days of CIP exposure suggested reactive oxygen species overproduction and thus the generation of oxidatively damaged proteins (e.g., carbonylated proteins) in the earthworms. Under mild CIP stress, the 20S proteasome was capable of degrading most of the damaged proteins independent of ubiquitin...
August 29, 2017: Science of the Total Environment
Xiaorong Wang, Ilan E Chemmama, Clinton Yu, Alexander Huszagh, Yue Xu, Rosa Viner, Sarah A Block, Peter Cimermancic, Scott D Rychnovsky, Yihong Ye, Andrej Sali, Lan Huang
Oxidative stress has been implicated in multiple human neurological and other disorders. Proteasomes are multi-subunit proteases critical for the removal of oxidatively damaged proteins. To understand stress-associated human pathologies, it is important to uncover the molecular events underlying the regulation of proteasomes upon oxidative stress. To this end, we investigated H2O2 stress-induced molecular changes of the human 26S proteasome and determined that stress-induced 26S proteasome disassembly is conserved from yeast to human...
September 29, 2017: Journal of Biological Chemistry
Julia Witkowska, Małgorzata Giżyńska, Przemysław Grudnik, Przemysław Golik, Przemysław Karpowicz, Artur Giełdoń, Grzegorz Dubin, Elżbieta Jankowska
Proteasomes are responsible for protein turnover in eukaryotic cells, degrading short-lived species but also removing improperly folded or oxidatively damaged ones. Dysfunction of a proteasome results in gradual accumulation of misfolded/damaged proteins, leading to their aggregation. It has been postulated that proteasome activators may facilitate removal of such aggregation-prone proteins and thus prevent development of neurodegenerative disorders. However, the discovery of pharmacologically relevant compounds is hindered by insufficient structural understanding of the activation process...
July 21, 2017: Scientific Reports
Barbara A Zieba, Laurent Henry, Matthieu Lacroix, Mohamed Jemaà, Thierry Lavabre-Bertrand, Laurent Meunier, Olivier Coux, Pierre-Emmanuel Stoebner
BACKGROUND: The ubiquitin proteasome pathway is involved in the pathogenesis of psoriasis and proteasome subunits are increased in lesional psoriatic skin. Recent works have highlighted that proteasome levels can be regulated through modulation of proteasome assembly notably by the proteasome maturation protein POMP. OBJECTIVES: To investigate whether proteasome assembly and POMP expression are modified in psoriatic skin. METHODS: Proteasome assembly as well as expression of proteasome regulators were assessed in non-lesional and lesional psoriatic skin using native gel electrophoresis and western blots respectively...
October 2017: Journal of Dermatological Science
Corey L Jones, Evert Njomen, Benita Sjögren, Thomas S Dexheimer, Jetze J Tepe
The 20S proteasome is the main protease for the degradation of oxidatively damaged and intrinsically disordered proteins. When accumulation of disordered or oxidatively damaged proteins exceeds proper clearance in neurons, imbalanced pathway signaling or aggregation occurs, which have been implicated in the pathogenesis of several neurological disorders. Screening of the NIH Clinical Collection and Prestwick libraries identified the neuroleptic agent chlorpromazine as a lead agent capable of enhancing 20S proteasome activity...
September 15, 2017: ACS Chemical Biology
Masatoshi Esaki, Md Tanvir Islam, Naoki Tani, Teru Ogura
Yeast Cdc48 is a well-conserved, essential chaperone of ATPases associated with diverse cellular activity (AAA) proteins, which recognizes substrate proteins and modulates their conformations to carry out many cellular processes. However, the fundamental mechanisms underlying the diverse pivotal roles of Cdc48 remain unknown. Almost all AAA proteins form a ring-shaped structure with a conserved aromatic amino acid residue that is essential for proper function. The threading mechanism hypothesis suggests that this residue guides the intrusion of substrate proteins into a narrow pore of the AAA ring, thereby becoming unfolded...
July 14, 2017: Scientific Reports
Udin Bahrudin, Masaki Unno, Kazuya Nishio, Akiko Kita, Peili Li, Masaru Kato, Masashi Inoue, Shunichi Tsujitani, Takuto Murakami, Rina Sugiyama, Yasushi Saeki, Yuji Obara, Keiji Tanaka, Hiroshi Yamaguchi, Isao Sakane, Yasushi Kawata, Toshiyuki Itoh, Haruaki Ninomiya, Ichiro Hisatome, Yukio Morimoto
Local anesthetics (LAs) inhibit endoplasmic reticulum-associated protein degradation, however the mechanisms remain elusive. Here, we show that the clinically used LAs pilsicainide and lidocaine bind directly to the 20S proteasome and inhibit its activity. Molecular dynamic calculation indicated that these LAs were bound to the β5 subunit of the 20S proteasome, and not to the other active subunits, β1 and β2. Consistently, pilsicainide inhibited only chymotrypsin-like activity, whereas it did not inhibit the caspase-like and trypsin-like activities...
July 11, 2017: Scientific Reports
Mohamed Amine Zaouali, Arnau Panisello-Roselló, Alexandre Lopez, Carlos Castro Benítez, Emma Folch-Puy, Agustín García-Gil, Teresa Carbonell, René Adam, Joan Roselló-Catafau
AIM: To compare liver proteolysis and proteasome activation in steatotic liver grafts conserved in University of Wisconsin (UW) and Institut Georges Lopez-1 (IGL-1) solutions. METHODS: Fatty liver grafts from male obese Zücker rats were conserved in UW and IGL-1 solutions for 24 h at 4 °Cand subjected to "ex vivo" normo-thermic perfusion (2 h; 37 °C). Liver proteolysis in tissue specimens and perfusate was measured by reverse-phase high performance liquid chromatography...
June 21, 2017: World Journal of Gastroenterology: WJG
Xiaodong Zhang, Di Lin, Yueqin Lin, Hongqing Chen, Minghua Zou, Shan Zhong, Xuefeng Yi, Siqi Han
The proteasome beta-4 subunit is required for the assembly of 20S proteasome complex, forming a pivotal component for the ubiquitin-proteasome system. Emerging evidence indicates that proteasome beta-4 subunit may be involved in underlying progression and mechanisms of malignancies. However, the role of proteasome beta-4 subunit in melanoma is currently unknown. Here, we reported that proteasome beta-4 subunit was markedly upregulated in human melanoma tissues and cells, compared with normal skin samples. High proteasome beta-4 subunit levels were significantly associated with poor overall survival in patients with melanoma...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Sandra Götze, Reinhard Saborowski, Oliviert Martínez-Cruz, Adriana Muhlia-Almazán, Arturo Sánchez-Paz
Crustaceans are intensively farmed in aquaculture facilities where they are vulnerable to parasites, bacteria, or viruses, often severely compromising the rearing success. The ubiquitin-proteasome system (UPS) is crucial for the maintenance of cellular integrity. Analogous to higher vertebrates, the UPS of crustaceans may also play an important role in stress resistance and pathogen defense. We studied the general properties of the proteasome system in the hemocytes of the whiteleg shrimp, Penaeus vannamei, and the European brown shrimp Crangon crangon...
June 23, 2017: Cell Stress & Chaperones
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