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26S proteasome

Huizhen Fan, Chunyan Jiang, Baoyuan Zhong, Jianwen Sheng, Ting Chen, Qingqing Chen, Jingtao Li, Hongchuan Zhao
Matrine may be protective against colorectal cancer (CRC), but how it may work is unclear. Thus, we explored the underlying mechanisms of matrine in CRC. Matrine-related proteins and CRC-related genes and therapeutic targets of matrine in CRC were predicted using a network pharmacology approach. Five targets, including interleukin 6 (IL-6), the 26S proteasome, tumor necrosis factor alpha (TNF- α ), transforming growth factor beta 1 (TGF- β 1) and p53, and corresponding high-mobility group box 1 (HMGB1) signaling and T helper cell differentiation were thought to be associated with matrine's mechanism...
2018: Journal of Immunology Research
Srividya Gopalakrishnan, Harshavardhana H Ediga, S Sreenivasa Reddy, G Bhanuprakash Reddy, Ayesha Ismail
Altered activity of the proteolytic machine-the 26S proteasome is observed in many disease conditions. Hence, either inhibition or activation of the 26S proteasome is thought to be a novel therapy for treatment of certain diseases such as cancer and neurodegenerative disorders. In this study, we tested the potential of cinnamon and one of its active ingredients, procyanidin-B2 (PCB2), in inhibiting the catalytic activities of the proteasome and suppressing prostate cancer cell growth. Proteasome activities were measured using fluorogenic substrates specific for the different enzymatic activities of the 26S proteasome by flourometry...
March 14, 2018: IUBMB Life
Yasukazu Takanezawa, Ryosuke Nakamura, Yuka Kojima, Yuka Sone, Shimpei Uraguchi, Masako Kiyono
Cancer cells enhance autophagic activity as a survival measure against metabolic and therapeutic stresses. The inhibition of autophagy may represent a valuable sensitizing target for cancer treatment. Recently, we examined the ability of various cytochalasins to inhibit autophagy and demonstrated the potent inhibitory effect of cytochalasin E (CE) on autophagic flux. The present study was conducted to investigate whether CE inhibited autophagosome-lysosome fusion, and to determine whether CE enhanced chemotherapy-induced cell death...
March 7, 2018: Biochemical and Biophysical Research Communications
Edmond Y Huang, Milton To, Erica Tran, Lorraine T Ador Dionisio, Hyejin J Cho, Katherine L M Baney, Camille I Pataki, James A Olzmann
Endoplasmic reticulum (ER)-associated degradation (ERAD) mediates the proteasomal clearance of proteins from the early secretory pathway. In this process, ubiquitinated substrates are extracted from membrane-embedded dislocation complexes by the AAA ATPase VCP and targeted to the cytosolic 26S proteasome. In addition to its well-established role in the degradation of misfolded proteins, ERAD also regulates the abundance of key proteins such as enzymes involved in cholesterol synthesis. However, due to the lack of generalizable methods, our understanding of the scope of proteins targeted by ERAD remains limited...
March 7, 2018: Molecular Biology of the Cell
Ganapathi Kandasamy, Claes Andréasson
In protein quality control, proteotoxic misfolded proteins are recognized by molecular chaperones, ubiquitylated by dedicated quality-control ligases and delivered to 26S proteasome for degradation. The chaperone Hsp70 and its nucleotide exchange factor Hsp110 functions in the degradation of misfolded proteins by the ubiquitin-proteasome system via poorly understood mechanisms. Here we report that yeast Hsp110 (Sse1 and Sse2) functions in the degradation of Hsp70-associated ubiquitin conjugates at the post-ubiquitylation step and is required for the proteasomal degradation of ubiquitin-independent substrates...
March 5, 2018: Journal of Cell Science
Martín Hugo, Ioanna Korovila, Markus Köhler, Carlos García-García, J Daniel Cabrera-García, Anabel Marina, Antonio Martínez-Ruiz, Tilman Grune
Under oxidative stress 26S proteasomes suffer reversible disassembly into its 20S and 19S subunits, a process mediated by HSP70. This inhibits the degradation of polyubiquitinated proteins by the 26S proteasome and allows the degradation of oxidized proteins by a free 20S proteasome. Low fluxes of antimycin A-stimulated ROS production caused dimerization of mitochondrial peroxiredoxin 3 and cytosolic peroxiredoxin 2, but not peroxiredoxin overoxidation and overall oxidation of cellular protein thiols. This moderate redox imbalance was sufficient to inhibit the ATP stimulation of 26S proteasome activity...
February 22, 2018: Redox Biology
Elan W Silverblatt-Buser, Melissa A Frick, Christina Rabeler, Nicholas J Kaplinsky
Protein folding and degradation are both required for protein quality control, an essential cellular activity that underlies normal growth and development. We investigated how BOB1 , an Arabidopsis thaliana small heat shock protein, maintains normal plant development. bob1 mutants exhibit organ polarity defects and have expanded domains of KNOX gene expression. Some of these phenotypes are ecotype specific suggesting that other genes function to modify them. Using a reverse genetic approach we identified an interaction between BOB1 and FIL , a gene required for abaxial organ identity...
February 27, 2018: G3: Genes—Genomes—Genetics
Bianca Baudisch, Ingrid Pfort, Eberhard Sorge, Udo Conrad
Here, we present data showing the directed degradation of target proteins recognized by a specific nanobody in transgenic plants. Green fluorescent protein was depleted by a chimeric nanobody fused to a distinct F-box domain, which enables protein degradation via the ubiquitin proteasome pathway. This technique could thus be used to knock out other proteins of interest in planta using specific, high-affinity binding proteins.
2018: Frontiers in Plant Science
Wenhao Zhao, Yinghua Ji, Shuhua Wu, Xiaofang Ma, Shuo Li, Feng Sun, Zhaobang Cheng, Yijun Zhou, Yongjian Fan
The V2 protein encoded by Begomovirus is essential for virus infection and is involved in multiple functions, such as virus movement and suppression of the host defence response. In this study, we reported that V2 encoded by the Tomato yellow leaf curl virus (TYLCV), which is one of the most devastating tomato-infecting begomoviruses, could interact with itself and a S71A mutation of V2 (V2S71A ) abolished its self-interaction. Fluorescence results showed that V2 localized primarily in the cytoplasm and around the nucleus...
February 23, 2018: Scientific Reports
Marieke Dubois, Katia Selden, Alexis Bediée, Gaëlle Rolland, Nicolas Baumberger, Sandra Noir, Lien Bach, Geneviève Lamy, Christine Granier, Pascal Genschik
The plant cell cycle is tightly regulated by factors that integrate endogenous cues and environmental signals to adapt plant growth to changing conditions. Under drought, cell division in young leaves is blocked by an active mechanism, reducing the evaporative surface and conserving energy resources. The molecular function of cyclin-dependent kinase-inhibitory proteins (CKIs) in regulating the cell cycle has already been well studied, but little is known about their involvement in cell cycle regulation under adverse growth conditions...
February 22, 2018: Plant Physiology
Divya Nedungadi, Anupama Binoy, Nanjan Pandurangan, Sanjay Pal, Bipin G Nair, Nandita Mishra
An α, β-unsaturated carbonyl compound of ginger, 6-Shogaol (6S), induced extensive cytoplasmic vacuolation and cell death in breast cancer cell (MDA-MB-231) and non-small lung cancer (A549) cells. In the presence of autophagic inhibitors the cells continued to exhibit cytoplasmic vacuolation and cell death clearly distinguishing it from the classic autophagic process. 6S induced death did not exhibit the characteristic apoptotic features like caspase cleavage, phosphatidyl serine exposure and DNA fragmentation...
February 17, 2018: Experimental Cell Research
D S Liyanage, W K M Omeka, G I Godahewa, Jehee Lee
Thioredoxin is a highly conserved protein found in both prokaryotes and eukaryotes. Reactive oxygen species (ROS) are produced in response to metabolic processes, radiation, metal oxidation, and pathological infections. High levels of ROS lead to cell death via autophagy. However, thioredoxin acts as an active regulatory enzyme in response to excessive ROS. Here, we performed in-silico analysis, immune challenge experiments, and functional assays of seahorse thioredoxin-like protein 1 (ShTXNL1). Evolutionary identification showed that ShTXNL1 protein belongs to the thioredoxin superfamily comprising 289 amino acids...
February 7, 2018: Fish & Shellfish Immunology
Makoto Tanaka, Yunhao Zhu, Masafumi Shionyu, Nozomi Ota, Natsumi Shibata, Chihiro Watanabe, Akihito Mizusawa, Ryuzo Sasaki, Tamio Mizukami, Isamu Shiina, Makoto Hasegawa
Ridaifen-F (RID-F) potently inhibits proteolytic activities of the 20S proteasome but poorly inhibits those of the 26S proteasome. Here, we report preparation of several conjugates in which various peptides are connected to RID-F. Conjugates with peptides consisting of seven amino acid residues significantly inhibited the 26S proteasome. Particularly, RID-F conjugated to an octaarginine peptide (R8, a so-called cell-penetrating peptide) inhibited intracellular proteasome activities and induced cell death in drug-resistant KMS-11 myeloma cells...
January 31, 2018: European Journal of Medicinal Chemistry
Di Yun, Yinghan Zhuang, Michael R Kreutz, Thomas Behnisch
Posttranslational modification and degradation of proteins by the ubiquitin-proteasome system (UPS) is crucial to synaptic transmission. It is well established that 19S proteasome associated deubiquitinases (DUBs) reverse the process of ubiquitination by removing ubiquitin from their substrates. However, their potential contribution to hippocampal synaptic plasticity has not been addressed in detail. Here, we report that inhibition of the 19S proteasome associated DUBs, ubiquitin C-terminal hydrolase 5 (UCHL5) and ubiquitin-specific peptidase 14 (USP14) by b-AP15 results in an accumulation of polyubiquitinated proteins and a reduction of monomeric ubiquitin without overt effects on 26S proteasome activity...
January 30, 2018: Neuropharmacology
Emily Bergbower, Clement Boinot, Inna Sabirzhanova, William Guggino, Liudmila Cebotaru
BACKGROUND/AIMS: The CFTR-Associated Ligand (CAL), a PDZ domain containing protein with two coiled-coil domains, reduces cell surface WT CFTR through degradation in the lysosome by a well-characterized mechanism. However, CAL's regulatory effect on ΔF508 CFTR has remained almost entirely uninvestigated. METHODS: In this study, we describe a previously unknown pathway for CAL by which it regulates the membrane expression of ΔF508 CFTR through arrest of ΔF508 CFTR trafficking in the endoplasmic reticulum (ER) using a combination of cell biology, biochemistry and electrophysiology...
January 29, 2018: Cellular Physiology and Biochemistry
Miriam Kolog Gulko, Gabriele Heinrich, Carina Gross, Blagovesta Popova, Oliver Valerius, Piotr Neumann, Ralf Ficner, Gerhard H Braus
The transition from vegetative growth to multicellular development represents an evolutionary hallmark linked to an oxidative stress signal and controlled protein degradation. We identified the Sem1 proteasome subunit, which connects stress response and cellular differentiation. The sem1 gene encodes the fungal counterpart of the human Sem1 proteasome lid subunit and is essential for fungal cell differentiation and development. A sem1 deletion strain of the filamentous fungus Aspergillus nidulans is able to grow vegetatively and expresses an elevated degree of 20S proteasomes with multiplied ATP-independent catalytic activity compared to wildtype...
February 5, 2018: PLoS Genetics
Qiang Guo, Carina Lehmer, Antonio Martínez-Sánchez, Till Rudack, Florian Beck, Hannelore Hartmann, Manuela Pérez-Berlanga, Frédéric Frottin, Mark S Hipp, F Ulrich Hartl, Dieter Edbauer, Wolfgang Baumeister, Rubén Fernández-Busnadiego
Protein aggregation and dysfunction of the ubiquitin-proteasome system are hallmarks of many neurodegenerative diseases. Here, we address the elusive link between these phenomena by employing cryo-electron tomography to dissect the molecular architecture of protein aggregates within intact neurons at high resolution. We focus on the poly-Gly-Ala (poly-GA) aggregates resulting from aberrant translation of an expanded GGGGCC repeat in C9orf72, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia...
January 31, 2018: Cell
Cheng-Fei Li, Jia-Xing Sun, Yuan Gao, Fei Shi, Yi-Kai Pan, Yong-Chun Wang, Xi-Qing Sun
Individuals exposed to long-term spaceflight often experience cardiovascular dysfunctions characterized by orthostatic intolerance, disability on physical exercise, and even frank syncope. Recent studies have showed that the alterations of cardiovascular system are closely related to the functional changes of endothelial cells. We have shown previously that autophagy can be induced by simulated microgravity in human umbilical vein endothelial cells (HUVECs). However, the mechanism of enhanced autophagy induced by simulated microgravity and its role in the regulation of endothelial function still remain unclear...
February 2, 2018: Cell Death & Disease
Kaixuan Zhang, Maria D Logacheva, Yu Meng, Jianping Hu, Dongpu Wan, Long Li, Janovská Dagmar, Zhiyong Wang, Milen I Georgiev, Zhuo Yu, Fuyu Yang, Mingli Yan, Meiliang Zhou
Jasmonates (JAs) are plant hormones that induce many secondary metabolites accumulation, such as rutin in buckwheat, via regulation of JAs-responsive transcription factors (TFs). Here, we report on the identification of a clade of JAs-responsive subgroup 4 MYB TFs, FtMYB13, FtMYB14, FtMYB15 and FtMYB16, directly repressing rutin biosynthesis in Fagopyrum tataricum. Immunoblot analysis showed that FtMYB13, FtMYB14 and FtMYB15 could be degraded via 26S proteasome in COI1-dependent JA signaling pathway, and this degradation is due to the SID motif in their C-terminus...
January 31, 2018: Journal of Experimental Botany
Michal Zigo, Karl Kerns, Miriam Sutovsky, Peter Sutovsky
Protein ubiquitination is a stable, reversible post-translational modification, targeting proteins for degradation/recycling by the 26S proteasome in a well-characterized enzymatic cascade. Studies have revealed the role of UPS in the regulation of fertilization, including sperm-zona pellucida interactions and the early event of sperm capacitation. The present study investigates the changes in proteasome compartmentalization, subunit composition and post-translational modifications during in vitro capacitation of fresh boar spermatozoa...
January 29, 2018: Cell and Tissue Research
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