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20S proteasome

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https://www.readbyqxmd.com/read/28340042/effects-of-dietary-l-arginine-levels-on-small-intestine-protein-turnover-and-the-expression-of-genes-related-to-protein-synthesis-and-proteolysis-of-layers
#1
L P Miao, C Yuan, X Y Dong, X Y Zhang, M Y Zhou, X T Zou
The aim of this study was to test the effects of dietary L-arginine (Arg) levels on protein turnover in the small intestine and the expression of genes related to protein synthesis and proteolysis of laying hens. Xinyang Black commercial laying hens (n = 864, aged 217 d) were randomly distributed to 6 treatments with 4 replicates of 36 birds. The dietary treatments were corn-corn gluten meal based diets containing 0.64, 0.86, 1.03, 1.27, 1.42 and 1.66% L-Arg, respectively. Fractional protein synthesis rate (FSR) and fractional protein gain rate (FGR) in the jejunum were the highest in the 1...
March 9, 2017: Poultry Science
https://www.readbyqxmd.com/read/28322792/molecular-chaperones-of-the-hsp70-family-assist-in-the-assembly-of-20s-proteasomes
#2
Lindsay J Hammack, Kyle Firestone, William Chang, Andrew R Kusmierczyk
The eukaryotic 26S proteasome is a large protease comprised of two major sub assemblies, the 20S proteasome, or core particle (CP), and the 19S regulatory particle (RP). Assembly of the CP and RP is assisted by an expanding list of dedicated assembly factors. For the CP, this includes Ump1 and the heterodimeric Pba1-Pba2 and Pba3-Pba4 proteins. It is not known how many additional proteins that assist in proteasome biogenesis remain to be discovered. Here, we demonstrate that two members of the Hsp70 family in yeast, Ssa1 and Ssa2, play a direct role in CP assembly...
March 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28300624/neurotoxicity-of-the-steroidal-alkaloids-tomatine-and-tomatidine-is-rip1-kinase-and-caspase-independent-and-involves-the-eif2%C3%AE-branch-of-the-endoplasmic-reticulum
#3
Daniela Correia da Silva, Paula B Andrade, Patrícia Valentão, David M Pereira
Steroidal alkaloids are a class of natural products that occur in several species of the Solanaceae family. In the case of tomato plant (Lycopersicon esculentum Mill.), tomatine and its aglycone, tomatidine, are the most representative molecules. These steroidal alkaloids have already shown several potentially useful biological activities, from anticancer to anti-inflammatory or antibacterial. In this work, the toxicity of these molecules in neuronal cells, namely in the neuroblastoma cell line SH-SY5Y, was assessed, emphasis being given to the cellular mechanisms underlying the effects observed...
March 11, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28278207/pa28-modulates-antigen-processing-and-viral-replication-during-coxsackievirus-b3-infection
#4
Dorota Respondek, Martin Voss, Ina Kühlewindt, Karin Klingel, Elke Krüger, Antje Beling
The function of the proteasome is modulated at the level of subunit expression and by association with its regulatory complexes. During coxsackievirus B3 (CVB3) myocarditis, IFN-induced formation of immunoproteasomes (ip) is known to be critical for regulating immune modulating molecules. The function of the IFN-γ-inducible proteasome regulator subunits PA28 α and β, however, in this context was unknown. During viral myocarditis, we found an increased abundance of PA28β subunits in heart tissue. PA28α/β exists in PA28-20S-PA28 and PA700-20S-PA28 hybrid proteasome complexes in cells both with either predominant ip and standard proteasome (sp) expression...
2017: PloS One
https://www.readbyqxmd.com/read/28274691/anti-ageing-properties-of-khelma-longevity%C3%A2-treatment-of-human-fibroblasts-increases-proteasome-levels-and-decreases-the-levels-of-oxidized-proteins
#5
Konstantinos Voutetakis, Vasiliki Delitsikou, Michel Georges Magouritsas, Efstathios S Gonos
We have determined the putative anti-ageing properties of Khelma Longevity™, a formula based on various natural compounds from the Mediterranean area. Human primary fibroblast cultures were treated with a wide range of concentrations of Khelma Longevity™ for 1 day or 3 consecutive days. Following these treatments, two major and complementary biomarkers of ageing were measured, namely, the proteasome and the amount of oxidized proteins. It was observed that 24h of treatment with Khelma Longevity™ resulted in a maximum increase of about 41% of the total protein levels of 20S proteasome...
March 6, 2017: New Biotechnology
https://www.readbyqxmd.com/read/28263979/stress-induced-nqo1-controls-stability-of-c-ebp%C3%AE-against-20s-proteasomal-degradation-to-regulate-p63-expression-with-implications-in-protection-against-chemical-induced-skin-cancer
#6
https://www.readbyqxmd.com/read/28263975/disruption-of-nad-p-h-quinone-oxidoreductase-1-gene-in-mice-leads-to-20s-proteasomal-degradation-of-p63-resulting-in-thinning-of-epithelium-and-chemical-induced-skin-cancer
#7
https://www.readbyqxmd.com/read/28263418/crystal-structure-of-human-proteasome-assembly-chaperone-pac4-involved-in-proteasome-formation
#8
Eiji Kurimoto, Tadashi Satoh, Yuri Ito, Eri Ishihara, Kenta Okamoto, Maho Yagi-Utsumi, Keiji Tanaka, Koichi Kato
The 26S proteasome is a large protein complex, responsible for degradation of ubiquinated proteins in eukaryotic cells. Eukaryotic proteasome formation is a highly ordered process that is assisted by several assembly chaperones. The assembly of its catalytic 20S core particle depends on at least five proteasome-specific chaperones, i.e., proteasome-assembling chaperons 1-4 (PAC1-4) and proteasome maturation protein (POMP). The orthologues of yeast assembly chaperones have been structurally characterized, whereas most mammalian assembly chaperones are not...
March 6, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28245629/high-levels-of-serum-ubiquitin-and-proteasome-in-a-case-of-hla-b27-uveitis
#9
Settimio Rossi, Carlo Gesualdo, Rosa Maisto, Maria Consiglia Trotta, Nadia Di Carluccio, Annalisa Brigida, Valentina Di Iorio, Francesco Testa, Francesca Simonelli, Michele D'Amico, Clara Di Filippo
In this paper, the authors describe a case of high serum levels of ubiquitin and proteasome in a woman under an acute attack of autoimmune uveitis. The woman was 52 years old, diagnosed as positive for the Human leukocyte antigen-B27 gene, and came to our observation in January 2013 claiming a severe uveitis attack that involved the right eye. During the acute attack of uveitis, this woman had normal serum biochemical parameters but higher levels of serum ubiquitin and proteasome 20S subunit, with respect to a healthy volunteer matched for age and sex...
February 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28244987/capzimin-is-a-potent-and-specific-inhibitor-of-proteasome-isopeptidase-rpn11
#10
Jing Li, Tanya Yakushi, Francesco Parlati, Andrew L Mackinnon, Christian Perez, Yuyong Ma, Kyle P Carter, Sharon Colayco, Gavin Magnuson, Brock Brown, Kevin Nguyen, Stefan Vasile, Eigo Suyama, Layton H Smith, Eduard Sergienko, Anthony B Pinkerton, Thomas D Y Chung, Amy E Palmer, Ian Pass, Sonja Hess, Seth M Cohen, Raymond J Deshaies
The proteasome is a vital cellular machine that maintains protein homeostasis, which is of particular importance in multiple myeloma and possibly other cancers. Targeting of proteasome 20S peptidase activity with bortezomib and carfilzomib has been widely used to treat myeloma. However, not all patients respond to these compounds, and those who do eventually suffer relapse. Therefore, there is an urgent and unmet need to develop new drugs that target proteostasis through different mechanisms. We identified quinoline-8-thiol (8TQ) as a first-in-class inhibitor of the proteasome 19S subunit Rpn11...
February 28, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28243125/carfilzomib-boosted-combination-therapy-for-relapsed-multiple-myeloma
#11
REVIEW
Raphael E Steiner, Elisabet E Manasanch
Carfilzomib is a proteasome inhibitor that binds selectively and irreversibly to the 20S proteasome, the proteolytic core particle within the 26S proteasome, resulting in the accumulation of proteasome substrates and ultimately growth arrest and apoptosis of tumor cells. The development and ultimate approval of this medication by regulatory agencies has been an important step toward improving clinical outcomes in multiple myeloma. Although initially approved as a single agent for the treatment of multiply relapsed and/or refractory myeloma, in the USA, it is now widely used in the early relapse setting in combination with lenalidomide and dexamethasone...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28193903/structural-analysis-of-mycobacterium-tuberculosis-homologues-of-the-eukaryotic-proteasome-assembly-chaperone-2-pac2
#12
Lin Bai, Jordan B Jastrab, Marta Isasa, Kuan Hu, Hongjun Yu, Steven P Gygi, K Heran Darwin, Huilin Li
A previous bioinformatics analysis identified the Mycobacterium tuberculosis (M. tuberculosis) proteins Rv2125 and Rv2714 as orthologs of the eukaryotic proteasome assembly chaperone 2 (PAC2). We set out to investigate whether Rv2125 or Rv2714 could function in proteasome assembly. We solved the crystal structure of Rv2125 at 3.0 Å resolution, which showed an overall fold similar to that of the PAC2 family proteins that include the archaeal PbaB and the yeast Pba1. However, Rv2125 and Rv2714 formed trimers, whereas PbaB forms tetramers and Pba1 dimerizes with Pba2...
February 13, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28183185/rational-design-of-selective-and-bioactive-inhibitors-of-the-mycobacterium-tuberculosis-proteasome
#13
Kyle A Totaro, Dominik Barthelme, Peter T Simpson, Xiuju Jiang, Gang Lin, Carl F Nathan, Robert T Sauer, Jason K Sello
The 20S core particle of the proteasome in Mycobacterium tuberculosis (Mtb) is a promising, yet unconventional, drug target. This multimeric peptidase is not essential, yet degrades proteins that have become damaged and toxic via reactions with nitric oxide (and/or the associated reactive nitrogen intermediates) produced during the host immune response. Proteasome inhibitors could render Mtb susceptible to the immune system, but they would only be therapeutically viable if they do not inhibit the essential 20S counterpart in humans...
February 10, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28182990/design-synthesis-and-biological-evaluation-of-novel-non-peptide-boronic-acid-derivatives-as-proteasome-inhibitors
#14
Ying Ge, Aibo Li, Jianwei Wu, Haiwei Feng, Letian Wang, Hongwu Liu, Yungen Xu, Qingxiang Xu, Li Zhao, Yuyan Li
A novel series of non-peptide proteasome inhibitors bearing the 1, 4-naphthoquinone scaffold and boronic acid warhead was developed. In the biological evaluation on the chymotrypsin-like activity of human 20S proteasome, five compounds showed IC50 values in the nanomolar range. Docking experiments into the yeast 20S proteasome rationalized their biological activities and allowed further optimization of this interesting class of inhibitors. Within the cellular proliferation inhibition assay and western blot analysis, compound 3e demonstrated excellent anti-proliferative activity against solid tumor cells and clear accumulation of ubiquitinated cellular proteins...
January 23, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28177129/role-of-parp-activity-in-lung-cancer-induced-cachexia-effects-on-muscle-oxidative-stress-proteolysis-anabolic-markers-and-phenotype
#15
Alba Chacon-Cabrera, Mercè Mateu-Jimenez, Klaus Langohr, Clara Fermoselle, Elena García-Arumí, Antoni L Andreu, Jose Yelamos, Esther Barreiro
Strategies to treat cachexia are still at its infancy. Enhanced muscle protein breakdown and ubiquitin-proteasome system are common features of cachexia associated with chronic conditions including lung cancer (LC). Poly(ADP-ribose) polymerases (PARP), which play a major role in chromatin structure regulation, also underlie maintenance of muscle metabolism and body composition. We hypothesized that protein catabolism, proteolytic markers, muscle fiber phenotype, and muscle anabolism may improve in respiratory and limb muscles of LC-cachectic Parp-1-deficient (Parp-1(-/-) ) and Parp-2(-/-) mice...
February 8, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28165654/identification-of-proteasomal-catalytic-subunit-psma6-as-a-therapeutic-target-for-lung-cancer
#16
Tomohiko Kakumu, Mitsuo Sato, Daiki Goto, Toshio Kato, Naoyuki Yogo, Tetsunari Hase, Masahiro Morise, Takayuki Fukui, Kohei Yokoi, Yoshitaka Sekido, Luc Girard, John D Minna, Lauren A Byers, John V Heymach, Kevin R Coombes, Masashi Kondo, Yoshinori Hasegawa
To identify potential therapeutic targets for lung cancer, we performed semi-genome-wide shRNA screening combined with the utilisation of genome-wide expression and copy number data. shRNA screening targeting 5,043 genes in NCI-H460 identified 51 genes as candidates. Pathway analysis revealed that the 51 genes were enriched for the five pathways, including ribosome, proteasome, RNA polymerase, pyrimidine metabolism and spliceosome pathways. We focused on the proteasome pathway that involved six candidate genes because its activation has been demonstrated in diverse human malignancies, including lung cancer...
February 6, 2017: Cancer Science
https://www.readbyqxmd.com/read/28159760/nad-p-h-quinone-oxidoreductase-1-nqo1-competes-with-20s-proteasome-for-binding-with-c-ebp%C3%AE-leading-to-its-stabilization-and-protection-against-radiation-induced-myeloproliferative-disease
#17
https://www.readbyqxmd.com/read/28157553/immunoproteasome-subunit-deficiency-has-no-influence-on-the-canonical-pathway-of-nf-%C3%AE%C2%BAb-activation
#18
Annegret Bitzer, Michael Basler, Daniel Krappmann, Marcus Groettrup
Activation of the pro-inflammatory transcription factor NF-κB requires signal-induced proteasomal degradation of the inhibitor of NF-κB (IκB) in order to allow nuclear translocation. Most cell types are capable of expressing two types of 20S proteasome core particles, the constitutive proteasome and immunoproteasome. Inducible under inflammatory conditions, the immunoproteasome is mainly characterized through an altered cleavage specificity compared to the constitutive proteasome. However, the question whether immunoproteasome subunits affect NF-κB signal transduction differently from constitutive subunits is still up for debate...
March 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28137628/effect-of-ionizing-radiation-exposure-on-trypanosoma-cruzi-ubiquitin-proteasome-system
#19
Paula G Cerqueira, Danielle G Passos-Silva, João P Vieira-da-Rocha, Isabela Cecilia Mendes, Karla A de Oliveira, Camila F B Oliveira, Liza F F Vilela, Ronaldo A P Nagem, Joseane Cardoso, Sheila C Nardelli, Marco A Krieger, Glória R Franco, Andrea M Macedo, Sérgio D J Pena, Sérgio Schenkman, Dawidson A Gomes, Renata Guerra-Sá, Carlos R Machado
In recent years, proteasome involvement in the damage response induced by ionizing radiation (IR) became evident. However, whether proteasome plays a direct or indirect role in IR-induced damage response still unclear. Trypanosoma cruzi is a human parasite capable of remarkable high tolerance to IR, suggesting a highly efficient damage response system. Here, we investigate the role of T. cruzi proteasome in the damage response induced by IR. We exposed epimastigotes to high doses of gamma ray and we analyzed the expression and subcellular localization of several components of the ubiquitin-proteasome system...
January 27, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28106073/high-resolution-cryo-em-structure-of-the-proteasome-in-complex-with-adp-alfx
#20
Zhanyu Ding, Zhenglin Fu, Cong Xu, Yifan Wang, Yanxing Wang, Junrui Li, Liangliang Kong, Jinhuan Chen, Na Li, Rongguang Zhang, Yao Cong
The 26S proteasome is an ATP-dependent dynamic 2.5 MDa protease that regulates numerous essential cellular functions through degradation of ubiquitinated substrates. Here we present a near-atomic-resolution cryo-EM map of the S. cerevisiae 26S proteasome in complex with ADP-AlFx. Our biochemical and structural data reveal that the proteasome-ADP-AlFx is in an activated state, displaying a distinct conformational configuration especially in the AAA-ATPase motor region. Noteworthy, this map demonstrates an asymmetric nucleotide binding pattern with four consecutive AAA-ATPase subunits bound with nucleotide...
March 2017: Cell Research
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