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Proteasome

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https://www.readbyqxmd.com/read/28346424/skp2-deficiency-restricts-the-progression-and-stem-cell-features-of-castration-resistant-prostate-cancer-by-destabilizing-twist
#1
D Ruan, J He, C-F Li, H-J Lee, J Liu, H-K Lin, C-H Chan
Castration-resistant prostate cancer (CRPC) remains a major clinical challenge because of the lack of effective targeted therapy for its treatment. The mechanism underlying how CRPC gains resistance toward hormone depletion and other forms of chemotherapy is poorly understood. Research on understanding the factors that drive these processes is desperately needed to generate new therapies to cure the disease. Here, we discovered a fundamental role of S-phase protein kinase 2 (Skp2) in the formation and progression of CRPC...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346422/the-metastatic-suppressor-ndrg1-inhibits-emt-migration-and-invasion-through-interaction-and-promotion-of-caveolin-1-ubiquitylation-in-human-colorectal-cancer-cells
#2
L Mi, F Zhu, X Yang, J Lu, Y Zheng, Q Zhao, X Wen, A Lu, M Wang, M Zheng, J Ji, J Sun
N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28345458/proteasome-expression-and-activity-in-cancer-and-cancer-stem-cells
#3
Ioannis A Voutsadakis
Proteasome is a multi-protein organelle that participates in cellular proteostasis by destroying damaged or short-lived proteins in an organized manner guided by the ubiquitination signal. By being in a central place in the cellular protein complement homeostasis, proteasome is involved in virtually all cell processes including decisions on cell survival or death, cell cycle, and differentiation. These processes are important also in cancer, and thus, the proteasome is an important regulator of carcinogenesis...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28344832/in-silico-functional-elucidation-of-uncharacterized-proteins-of-chlamydia-abortus-strain-llg
#4
Gagandeep Singh, Dixit Sharma, Vikram Singh, Jyoti Rani, Francessco Marotta, Manoj Kumar, Gorakh Mal, Birbal Singh
AIM: This study reports structural modeling, molecular dynamics profiling of hypothetical proteins in Chlamydia abortus genome database. METHODOLOGY: The hypothetical protein sequences were extracted from C. abortus LLG Genome Database for functional elucidation using in silico methods. RESULTS: Fifty-one proteins with their roles in defense, binding and transporting other biomolecules were unraveled. Forty-five proteins were found to be nonhomologous to proteins present in hosts infected by C...
March 2017: Future Science OA
https://www.readbyqxmd.com/read/28343904/clinical-and-serologic-responses-after-a-two-dose-series-of-high-dose-influenza-vaccine-in-plasma-cell-disorders-a-prospective-single-arm-trial
#5
Andrew R Branagan, Eamon Duffy, Randy A Albrecht, Dennis L Cooper, Stuart Seropian, Terri L Parker, Geliang Gan, Fangyong Li, Daniel Zelterman, Chandra Sekhar Boddupalli, Lin Zhang, Rakesh Verma, Thomas M Ferencz, Madhav V Dhodapkar
BACKGROUND: Patients with multiple myeloma (MM) and other plasma cell disorders are highly susceptible to influenza infections, which are major causes of morbidity in this population, despite the routine administration of a seasonal influenza vaccination. Existing data are limited by small and retrospective studies, which suggest poor seroprotection rates of < 20% after standard influenza vaccination in patients with MM. PATIENTS AND METHODS: Patients with plasma cell dyscrasia (n = 51) were treated with a 2-dose series of high-dose inactivated trivalent influenza vaccine during the 2014 to 2015 influenza season...
March 7, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28343629/biallelic-variants-in-otud6b-cause-an-intellectual-disability-syndrome-associated-with-seizures-and-dysmorphic-features
#6
Teresa Santiago-Sim, Lindsay C Burrage, Frédéric Ebstein, Mari J Tokita, Marcus Miller, Weimin Bi, Alicia A Braxton, Jill A Rosenfeld, Maher Shahrour, Andrea Lehmann, Benjamin Cogné, Sébastien Küry, Thomas Besnard, Bertrand Isidor, Stéphane Bézieau, Isabelle Hazart, Honey Nagakura, LaDonna L Immken, Rebecca O Littlejohn, Elizabeth Roeder, Bulent Kara, Katia Hardies, Sarah Weckhuysen, Patrick May, Johannes R Lemke, Orly Elpeleg, Bassam Abu-Libdeh, Kiely N James, Jennifer L Silhavy, Mahmoud Y Issa, Maha S Zaki, Joseph G Gleeson, John R Seavitt, Mary E Dickinson, M Cecilia Ljungberg, Sara Wells, Sara J Johnson, Lydia Teboul, Christine M Eng, Yaping Yang, Peter-Michael Kloetzel, Jason D Heaney, Magdalena A Walkiewicz
Ubiquitination is a posttranslational modification that regulates many cellular processes including protein degradation, intracellular trafficking, cell signaling, and protein-protein interactions. Deubiquitinating enzymes (DUBs), which reverse the process of ubiquitination, are important regulators of the ubiquitin system. OTUD6B encodes a member of the ovarian tumor domain (OTU)-containing subfamily of deubiquitinating enzymes. Herein, we report biallelic pathogenic variants in OTUD6B in 12 individuals from 6 independent families with an intellectual disability syndrome associated with seizures and dysmorphic features...
March 21, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28343271/protein-degradation-systems-in-the-skeletal-muscles-of-parr-and-smolt-atlantic-salmon-salmo-salar-l-and-brown-trout-salmo-trutta-l
#7
Nadezda P Kantserova, Liudmila A Lysenko, Alexey E Veselov, Nina N Nemova
Although protein degradation limits the rate of muscle growth in fish, the role of proteolytic systems responsible for degrading myofibrillar proteins in skeletal muscle is not well defined. The study herein aims to evaluate the role of calpains (calcium-activated proteases) and proteasomes (ATP-dependent proteases) in mediating muscle protein turnover at different life stages in wild salmonids. Protease activities were estimated in Atlantic salmon (Salmo salar L.) and brown trout (Salmo trutta L.) parr and smolts from the Indera River (Kola Peninsula, Russia)...
March 26, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28342806/molecular-regulation-of-mitochondrial-dynamics-in-cardiac-disease
#8
REVIEW
Jinliang Nan, Wei Zhu, M S Rahman, Mingfei Liu, Dan Li, Shengan Su, Na Zhang, Xinyang Hu, Hong Yu, Mahesh P Gupta, Jian''an Wang
Mitochondrial homeostasis is critical for keeping functional heart in response to metabolic or environmental stresses. Mitochondrial fission and fusion (mitochondrial dynamics) play essential roles in maintaining mitochondrial homeostasis, defects in mitochondrial dynamics lead to cardiac diseases such as ischemia-reperfusion injury (IRI), heart failure and diabetic cardiomyopathy. Mitochondrial dynamics is determined by mitochondrial fission and fusion proteins, including OPA1, mitofusins and Drp1. These proteins are tightly regulated by a series of signaling pathways through different aspects such as transcription, post translation modifications (PTMs) and proteasome-dependent protein degradation...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342223/ritonavir-and-ixazomib-kill-bladder-cancer-cells-by-causing-ubiquitinated-protein-accumulation
#9
Akinori Sato, Takako Asano, Kazuki Okubo, Makoto Isono, Tomohiko Asano
There is no curative treatment for advanced bladder cancer. Causing ubiquitinated protein accumulation and endoplasmic reticulum (ER) stress is a novel approach to cancer treatment. The human immunodeficiency virus protease inhibitor ritonavir has been reported to suppress heat shock protein 90 and increase the amount of unfolded proteins in the cell. If the proteasome functions normally, however, they are rapidly degraded. We postulated that the novel proteasome inhibitor ixazomib combined with ritonavir would kill bladder cancer cells effectively by inhibiting degradation of these unfolded proteins and thereby causing ubiquitinated proteins to accumulate...
March 25, 2017: Cancer Science
https://www.readbyqxmd.com/read/28341998/ire1-signaling-exacerbates-alzheimer-s-disease-pathogenesis
#10
Claudia Duran-Aniotz, Victor Hugo Cornejo, Sandra Espinoza, Álvaro O Ardiles, Danilo B Medinas, Claudia Salazar, Andrew Foley, Ivana Gajardo, Peter Thielen, Takao Iwawaki, Wiep Scheper, Claudio Soto, Adrian G Palacios, Jeroen J M Hoozemans, Claudio Hetz
Altered proteostasis is a salient feature of Alzheimer's disease (AD), highlighting the occurrence of endoplasmic reticulum (ER) stress and abnormal protein aggregation. ER stress triggers the activation of the unfolded protein response (UPR), a signaling pathway that enforces adaptive programs to sustain proteostasis or eliminate terminally damaged cells. IRE1 is an ER-located kinase and endoribonuclease that operates as a major stress transducer, mediating both adaptive and proapoptotic programs under ER stress...
March 24, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28341829/usp9x-deubiquitylating-enzyme-maintains-raptor-protein-levels-mtorc1-signalling-and-proliferation-in-neural-progenitors
#11
Caitlin R Bridges, Men-Chee Tan, Susitha Premarathne, Devathri Nanayakkara, Bernadette Bellette, Dusan Zencak, Deepti Domingo, Jozef Gecz, Mariyam Murtaza, Lachlan A Jolly, Stephen A Wood
USP9X, is highly expressed in neural progenitors and, essential for neural development in mice. In humans, mutations in USP9X are associated with neurodevelopmental disorders. To understand USP9X's role in neural progenitors, we studied the effects of altering its expression in both the human neural progenitor cell line, ReNcell VM, as well as neural stem and progenitor cells derived from Nestin-cre conditionally deleted Usp9x mice. Decreasing USP9X resulted in ReNcell VM cells arresting in G0 cell cycle phase, with a concomitant decrease in mTORC1 signalling, a major regulator of G0/G1 cell cycle progression...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28341633/increased-hypoxia-inducible-factor-in-the-muscles-of-tumor-bearing-mice
#12
Raymond Devine, Sabahattin Bicer, Peter J Reiser, Loren E Wold
Cancer cachexia is a progressive wasting disease resulting in significant effects on the quality of life and a high mortality. Most studies on cancer cachexia have focused on skeletal muscle; however, the heart is now recognized as a major site of cachexia-related effects. In order to elucidate possible mechanisms, a proteomic study was performed on the left ventricles of colon-26 adenocarcinoma tumor-bearing mice. The results revealed several changes in proteins involved in metabolism. An integrated pathway analysis of the results revealed a common mediator in hypoxia inducible factor-1α (HIF-1α)...
March 24, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28341300/a-phase-i-pharmacokinetic-study-of-intraperitoneal-bortezomib-and-carboplatin-in-patients-with-persistent-or-recurrent-ovarian-cancer-an-nrg-oncology-gynecologic-oncology-group-study
#13
Danielle A Jandial, William E Brady, Stephen B Howell, Heather A Lankes, Russell J Schilder, Jan H Beumer, Susan M Christner, Sandra Strychor, Matthew A Powell, Andrea R Hagemann, Kathleen N Moore, Joan L Walker, Paul A DiSilvestro, Linda R Duska, Paula M Fracasso, Don S Dizon
PURPOSE: Intraperitoneal (IP) therapy improves survival compared to intravenous (IV) treatment for women with newly diagnosed, optimally cytoreduced, ovarian cancer. However, the role of IP therapy in recurrent disease is unknown. Preclinical data demonstrated IP administration of the proteasome inhibitor, bortezomib prior to IP carboplatin increased tumor platinum accumulation resulting in synergistic cytotoxicity. We conducted this phase I trial of IP bortezomib and carboplatin in women with recurrent disease...
March 21, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28341100/the-ubiquitin-proteasome-system-a-potential-therapeutic-target-for-heart-failure
#14
Yaron D Barac, Fabian Emrich, Efrat Krutzwakd-Josefson, Sonja Schrepfer, Luiz C Sampaio, James T Willerson, Robert C Robbins, Aaron Ciechanover, Friedrich-Wilhelm Mohr, Dan Aravot, Doris A Taylor
The rising incidence of heart failure (HF) is one of the biggest challenges in cardiovascular medicine. The persistent shortage of donor organs for transplantation has led to an expanding application of left ventricular assist devices as a bridge to recovery. Accumulating evidence suggests that the ubiquitin-proteasome system (UPS), which is responsible for protein degradation, plays a direct role in cardiac hypertrophy and HF and is impacted by mechanical unloading. The UPS system also plays a role in the cardiac regulation of apoptosis, cell mass, and sarcomere quality control...
February 20, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28340282/carfilzomib-induces-leukaemia-cell-apoptosis-via-inhibiting-elk1-kiaa1524-elk-1-cip2a-and-activating-pp2a-not-related-to-proteasome-inhibition
#15
Chun-Yu Liu, Feng-Shu Hsieh, Pei-Yi Chu, Wen-Chun Tsai, Chun-Teng Huang, Yuan-Bin Yu, Tzu-Ting Huang, Po-Shen Ko, Man-Hsin Hung, Wan-Lun Wang, Chung-Wai Shiau, Kuen-Feng Chen
Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28340181/different-expression-patterns-of-sperm-motility-related-genes-in-testis-of-diploid-and-tetraploid-cyprinid-fish1
#16
Fangzhou Hu, Kang Xu, Yunfan Zhou, Chang Wu, Shi Wang, Jun Xiao, Min Wen, Rurong Zhao, Kaikun Luo, Min Tao, Wei Duan, Shaojun Liu
Sperm motility is an important standard to measure the fertility of male. In our previous study, we found that the diploid spermatozoa from allotetraploid hybrid (4nAT) had longer durations of rapid and slow progressive motility than haploid spermatozoa from common carp (COC). In this study, to explore sperm motility-related molecular mechanisms, we compared the testis tissues transcriptomes from two years old male COC and 4nAT. The RNA-seq data revealed that 2985 genes were differentially expressed between COC and 4nAT, including 2216 up-regulated and 769 down-regulated genes in 4nAT...
March 7, 2017: Biology of Reproduction
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
#17
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/28338973/inflammation-autoimmunity-and-hypertension-the-essential-role-of-tissue-transglutaminase
#18
Chen Liu, Rodney E Kellems, Yang Xia
Inflammatory cytokines cause hypertension when introduced into animals. Additional evidence indicates that cytokines induce the production of autoantibodies that activate the AT1 angiotensin receptor (AT1R). Extensive evidence shows that these autoantibodies, termed AT1-AA, contribute to hypertension. We review here recent studies showing that cytokine-induced hypertension and AT1-AA production require the ubiquitous enzyme, tissue transglutaminase (TG2). We consider 3 mechanisms by which TG2 may contribute to hypertension...
March 13, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28338014/entropic-stabilization-of-a-deubiquitinase-provides-conformational-plasticity-and-slow-unfolding-kinetics-beneficial-for-functioning-on-the-proteasome
#19
Yun-Tzai Cloud Lee, Chia-Yun Chang, Szu-Yu Chen, Yun-Ru Pan, Meng-Ru Ho, Shang-Te Danny Hsu
Human ubiquitin C-terminal hydrolyase UCH-L5 is a topologically knotted deubiquitinase that is activated upon binding to the proteasome subunit Rpn13. The length of its intrinsically disordered cross-over loop is essential for substrate recognition. Here, we showed that the catalytic domain of UCH-L5 exhibits higher equilibrium folding stability with an unfolding rate on the scale of 10(-8) s(-1), over four orders of magnitudes slower than its paralogs, namely UCH-L1 and -L3, which have shorter cross-over loops...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28337817/the-cytotoxic-effects-of-camptothecin-and-mastoparan-on-the-unicellular-green-alga-chlamydomonas-reinhardtii
#20
Jürgen Voigt, Markus Morawski, Johannes Wöstemeyer
We have recently reported that protease inhibitors affecting the activity of the proteasome cause necrotic cell death in Chlamydomonas reinhardtii instead of inducing apoptosis as shown for some mammalian cell lines. Therefore, we have studied other well-known inducers of apoptosis in mammalian cells for their effects on C. reinhardtii cells. Mastoparan caused rapid cell death without a prominent lag-phase under all growth conditions, whereas the cytotoxic effect of the topoisomerase I inhibitor camptothecin exclusively occured during the cell-division phase...
March 24, 2017: Journal of Eukaryotic Microbiology
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