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ER-associated degradation

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https://www.readbyqxmd.com/read/29155878/irhom2-is-essential-for-innate-immunity-to-rna-virus-by-antagonizing-er-and-mitochondria-associated-degradation-of-visa
#1
Wei-Wei Luo, Shu Li, Chen Li, Zhou-Qin Zheng, Pan Cao, Zhen Tong, Huan Lian, Su-Yun Wang, Hong-Bing Shu, Yan-Yi Wang
VISA (also known as MAVS, IPS-1 and Cardif) is an essential adaptor protein in innate immune response to RNA virus. The protein level of VISA is delicately regulated before and after viral infection to ensure the optimal activation and timely termination of innate antiviral response. It has been reported that several E3 ubiquitin ligases can mediate the degradation of VISA, but how the stability of VISA is maintained before and after viral infection remains enigmatic. In this study, we found that the ER-associated inactive rhomboid protein 2 (iRhom2) plays an essential role in mounting an efficient innate immune response to RNA virus by maintaining the stability of VISA through distinct mechanisms...
November 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29152155/chibby-1-a-new-component-of-%C3%AE-catenin-signaling-in-chronic-myeloid-leukemia
#2
REVIEW
Manuela Mancini, Simona Soverini, Gabriele Gugliotta, Maria Alessandra Santucci, Gianantonio Rosti, Michele Cavo, Giovanni Martinelli, Fausto Castagnetti
Chibby 1 (CBY1) is a small and evolutionarily conserved protein, which act as β-catenin antagonist. CBY1 is encoded by C22orf2 (22q13.1) Its antagonistic function on β-catenin involves the direct interaction with: The C-terminal activation domain of β-catenin, which hinders β-catenin binding with Tcf/Lef transcription factors hence repressing β-catenin transcriptional activation. 14-3-3 scaffolding proteins (σ or ξ), which drive CBY1 nuclear export into a stable tripartite complex with β-catenin. The relative proximity of C22orf2 gene encoding for CBY1 to the BCR breakpoint on chromosome 22q11, whose translocation and rearrangement with the c-ABL is the causative event of chronic myeloid leukemia (CML), suggested that gene haploinsufficiency may play a role in the disease pathogenesis and progression...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29144457/a-ubiquitin-dependent-signalling-axis-specific-for-alkbh-mediated-dna-dealkylation-repair
#3
Joshua R Brickner, Jennifer M Soll, Patrick M Lombardi, Cathrine B Vågbø, Miranda C Mudge, Clement Oyeniran, Renana Rabe, Jessica Jackson, Meagan E Sullender, Elyse Blazosky, Andrea K Byrum, Yu Zhao, Mark A Corbett, Jozef Gécz, Michael Field, Alessandro Vindigni, Geir Slupphaug, Cynthia Wolberger, Nima Mosammaparast
DNA repair is essential to prevent the cytotoxic or mutagenic effects of various types of DNA lesions, which are sensed by distinct pathways to recruit repair factors specific to the damage type. Although biochemical mechanisms for repairing several forms of genomic insults are well understood, the upstream signalling pathways that trigger repair are established for only certain types of damage, such as double-stranded breaks and interstrand crosslinks. Understanding the upstream signalling events that mediate recognition and repair of DNA alkylation damage is particularly important, since alkylation chemotherapy is one of the most widely used systemic modalities for cancer treatment and because environmental chemicals may trigger DNA alkylation...
November 16, 2017: Nature
https://www.readbyqxmd.com/read/29135079/cigarette-smoke-extract-and-isoprene-resulted-in-the-induction-of-apoptosis-and-autophagy-in-human-placenta-choriocarcinoma-jeg-3-cells
#4
Hae-Miru Lee, Kyung-Chul Choi
In this study, the effects of cigarette smoke (CS) on the induction of apoptosis via reactive oxygen species (ROS) production and endoplasmic reticulum stress (ER stress) of JEG-3 human choriocarcinoma cells were examined to confirm the relationship between CS and placenta development. Upon TUNEL assay, CS extract (3R4F; 0.3 and 2.1 μM) increased JEG-3 apoptosis. Western blot assay revealed that the protein expressions of p53, Bax, and CCAAT-enhancer-binding protein homologous protein (CHOP) increased, while the levels of Bcl-2 were reduced following CS extract treatment...
November 14, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29133892/er-associated-degradation-regulates-alzheimer-s-amyloid-pathology-and-memory-function-by-modulating-%C3%AE-secretase-activity
#5
Bing Zhu, LuLin Jiang, Timothy Huang, Yingjun Zhao, Tongfei Liu, Yongwang Zhong, Xiaoguang Li, Alexandre Campos, Kenneth Pomeroy, Eliezer Masliah, Dongxian Zhang, Huaxi Xu
Endoplasmic-reticulum-associated degradation (ERAD) is an important protein quality control system which maintains protein homeostasis. Constituents of the ERAD complex and its role in neurodegeneration are not yet fully understood. Here, using proteomic and FRET analyses, we demonstrate that the ER protein membralin is an ERAD component, which mediates degradation of ER luminal and membrane substrates. Interestingly, we identify nicastrin, a key component of the γ-secretase complex, as a membralin binding protein and membralin-associated ERAD substrate...
November 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29117944/small-molecule-sigma1-modulator-induces-autophagic-degradation-of-pd-l1
#6
Christina M Maher, Jeffrey D Thomas, Derick A Haas, Charles G Longen, Halley M Oyer, Jane Y Tong, Felix J Kim
Emerging evidence suggests that Sigma1 (SIGMAR1, also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small molecule modulators of Sigma1 alter endoplasmic reticulum (ER) associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type 1 integral membrane glycoprotein that is co-translationally inserted into the ER and is processed and transported through the secretory pathway...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29109534/natural-history-of-helicobacter-pylori-vaca-toxin-in-human-gastric-epithelium-in-vivo-vacuoles-and-beyond
#7
Vittorio Necchi, Patrizia Sommi, Alessandro Vanoli, Roberto Fiocca, Vittorio Ricci, Enrico Solcia
Uptake, intracellular trafficking and pathologic effects of VacA toxin from Helicobacter pylori have been widely investigated in vitro. However, no systematic analysis investigated VacA intracellular distribution and fate in H. pylori-infected human gastric epithelium in vivo, using ultrastructural immunocytochemistry that combines precise toxin localization with analysis of the overall cell ultrastructure and intercompartimental/interorganellar relationships. By immunogold procedure, in this study we investigated gastric biopsies taken from dyspeptic patients to characterize the overall toxin's journey inside human gastric epithelial cells in vivo...
November 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29109174/orientia-tsutsugamushi-modulates-endoplasmic-reticulum-associated-degradation-to-benefit-its-growth
#8
Kyle G Rodino, Lauren VieBrock, Sean M Evans, Hong Ge, Allen L Richards, Jason A Carlyon
Orientia tsutsugamushi, an obligate intracellular bacterium that is auxotrophic for the aromatic amino acids and histidine, causes scrub typhus, a potentially deadly infection that threatens one billion people. O. tsutsugamushi growth is minimal during the first 24 to 48 h of infection, but becomes logarithmic thereafter. How the pathogen modulates cellular functions to support its growth is poorly understood. The unfolded protein response (UPR) is a cytoprotective pathway that relieves endoplasmic reticulum (ER) stress by promoting ER-associated degradation (ERAD) of misfolded proteins...
November 6, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/29107682/underlying-mechanisms-for-sterol-induced-ubiquitination-and-er-associated-degradation-of-hmg-coa-reductase
#9
REVIEW
Brittany M Johnson, Russell A DeBose-Boyd
Accelerated ubiquitination and subsequent endoplasmic reticulum (ER)-associated degradation (ERAD) constitute one of several mechanisms for feedback control of HMG CoA reductase, the rate-limiting enzyme in synthesis of cholesterol and nonsterol isoprenoids. This ERAD is initiated by the accumulation of certain sterols in ER membranes, which trigger binding of reductase to ER membrane proteins called Insigs. Insig-associated ubiquitin ligases facilitate ubiquitination of reductase, marking the enzyme for extraction across the ER membrane through a reaction that is augmented by nonsterol isoprenoids...
October 28, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29098149/regulation-of-ire1%C3%AE-by-the-small-molecule-inhibitor-4%C3%AE-8c-in-hepatoma-cells
#10
Claire Stewart, Andrea Estrada, Paul Kim, Dong Wang, Yuren Wei, Chris Gentile, Michael Pagliassotti
The unfolded protein response (UPR) is activated in response to impairments of the folding environment in the endoplasmic reticulum (ER). The most conserved arm of the UPR, inositol-requiring ER-to-nucleus signaling protein (IRE1α), has been linked to the regulation of a diverse array of cellular processes including ER-associated degradation, inflammatory signaling, cell proliferation and membrane biogenesis. Recent studies have utilized the selective, small molecule inhibitor, 4μ8c, to examine the role of IRE1α endoribonuclease (RNase) activity in various cell types including multiple myeloma, mouse embryonic fibroblasts and pancreatic beta cells [1-5]...
April 2017: Endoplasmic Reticulum Stress in Diseases
https://www.readbyqxmd.com/read/29080872/-proteomic-profiling-of-hacat-keratinocytes-exposed-to-skin-damaging-detergents
#11
A L Rusanov, N A Petushkova, E V Poverennaya, K V Nakhod, O V Larina, A V Lisitsa, N G Luzgina
The effects of sodium dodecyl sulfate (25 mg/ml) and Triton X-100 (12.5 mg/ml and 25 mg/ml) on the HaCaT immortalized keratinocytes exposed to these surfactants for 48 h were studied. Using shotgun proteomics, a comparative analysis of the proteomic profiles of control and experimental cells after surfactants exposure was carried out. 260 common proteins were identified in control and experimental cells; 33 proteins were found in cells exposed to all three treatments, but not in control cells. These 33 proteins apparently reflect a nonspecific (universal) response of cells to toxic damage by the surfactants...
October 2017: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/29066441/endoplasmic-reticulum-stress-is-associated-with-autophagy-and-cardiomyocyte-remodeling-in-experimental-and-human-atrial-fibrillation
#12
Marit Wiersma, Roelien A M Meijering, Xiao-Yan Qi, Deli Zhang, Tao Liu, Femke Hoogstra-Berends, Ody C M Sibon, Robert H Henning, Stanley Nattel, Bianca J J M Brundel
BACKGROUND: Derailment of proteostasis, the homeostasis of production, function, and breakdown of proteins, contributes importantly to the self-perpetuating nature of atrial fibrillation (AF), the most common heart rhythm disorder in humans. Autophagy plays an important role in proteostasis by degrading aberrant proteins and organelles. Herein, we investigated the role of autophagy and its activation pathway in experimental and clinical AF. METHODS AND RESULTS: Tachypacing of HL-1 atrial cardiomyocytes causes a gradual and significant activation of autophagy, as evidenced by enhanced LC3B-II expression, autophagic flux and autophagosome formation, and degradation of p62, resulting in reduction of Ca(2+) amplitude...
October 24, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29059380/expression-of-arabidopsis-class-1-phytoglobin-atpgb1-delays-death-and-degradation-of-the-root-apical-meristem-during-severe-peg-induced-water-deficit
#13
Mohamed M Mira, Shuanglong Huang, Karuna Kapoor, Cassandra Hammond, Robert D Hill, Claudio Stasolla, Ian Dodd
Maintenance of a functional root is fundamental to plant survival in response to some abiotic stresses, such as water deficit. In this study, we found that overexpression of Arabidopsis class 1 phytoglobin (AtPgb1) alleviated the growth retardation of polyethylene glycol (PEG)-induced water stress by reducing programmed cell death (PCD) associated with protein folding in the endoplasmic reticulum (ER). This was in contrast to PEG-stressed roots down-regulating AtPgb1 that exhibited extensive PCD and reduced expression of several attenuators of ER stress, including BAX Inhibitor-1 (BI-1)...
October 20, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29054272/insights-on-the-hla-binding-peptidome-in-cancer
#14
Douglas F Lake
The intracellular compartments for proteolytic antigen processing in tumor cells produce peptides that are presented by MHC molecules to T cells. But first, the ubiquitin ligase system tags defective, misfolded, aged, and unstable proteins for degradation through the proteasome. Ubiqitinated proteins are unfolded and fed into the barrel-shaped core of the proteasome where a collection of multiple different proteases cleave proteins into oligopeptides. After exiting the proteasome, these oligopeptides are either completely degraded into amino acids or trimmed at the N- and C-termini so that they bind to transporter associated with antigen processing (TAP)...
2017: Enzymes
https://www.readbyqxmd.com/read/29051727/syvn1-an-erad-e3-ubiquitin-ligase-is-involved-in-gabaa%C3%AE-1-degradation-associated-with-methamphetamine-induced-conditioned-place-preference
#15
Dong-Liang Jiao, Yan Chen, Yao Liu, Yun-Yue Ju, Jian-Dong Long, Jiang Du, Chang-Xi Yu, Yu-Jun Wang, Min Zhao, Jing-Gen Liu
Abuse of methamphetamine (METH), a powerful addictive amphetamine-type stimulants (ATS), is becoming a global public health problem. The gamma-aminobutyric acid (GABA)ergic system plays a critical role in METH use disorders. By using rat METH conditioned place preference (CPP) model, we previously demonstrated that METH-associated rewarding memory formation was associated with the reduction of GABAAα1 expression in the dorsal straitum (Dstr), however, the underlying mechanism was unclear. In the present study, we found that METH-induced CPP formation was accompanied by a significant increase in the expression of Synovial apoptosis inhibitor 1 (SYVN1), an endoplasmic reticulum (ER)-associated degradation (ERAD) E3 ubiquitin ligase, in the Dstr...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29048431/hspb1-facilitates-erk-mediated-phosphorylation-and-degradation-of-bim-to-attenuate-endoplasmic-reticulum-stress-induced-apoptosis
#16
Donna Kennedy, Katarzyna Mnich, Deepu Oommen, Reka Chakravarthy, Leonardo Almeida-Souza, Michiel Krols, Svetlana Saveljeva, Karen Doyle, Sanjeev Gupta, Vincent Timmerman, Sophie Janssens, Adrienne M Gorman, Afshin Samali
BIM, a pro-apoptotic BH3-only protein, is a key regulator of the intrinsic (or mitochondrial) apoptosis pathway. Here, we show that BIM induction by endoplasmic reticulum (ER) stress is suppressed in rat PC12 cells overexpressing heat shock protein B1 (HSPB1 or HSP27) and that this is due to enhanced proteasomal degradation of BIM. HSPB1 and BIM form a complex that immunoprecipitates with p-ERK1/2. We found that HSPB1-mediated proteasomal degradation of BIM is dependent on MEK-ERK signaling. Other studies have shown that several missense mutations in HSPB1 cause the peripheral neuropathy, Charcot-Marie-Tooth (CMT) disease, which is associated with nerve degeneration...
August 31, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29046440/innate-sensing-of-influenza-a-virus-hemagglutinin-glycoproteins-by-the-host-endoplasmic-reticulum-er-stress-pathway-triggers-a-potent-antiviral-response-via-er-associated-protein-degradation
#17
Dylan A Frabutt, Bin Wang, Sana Riaz, Richard C Schwartz, Yong-Hui Zheng
Innate immunity provides an immediate defense against infection after host cells sense "danger" signals from microbes. Endoplasmic reticulum (ER) stress arises from accumulation of misfolded/unfolded proteins when protein load overwhelms the ER folding capacity, which activates the unfolded protein response (UPR) to restore the ER homeostasis. Here, we show that a mechanism for antiviral innate immunity is triggered after the ER stress pathway senses viral glycoproteins. When hemagglutinin (HA) glycoproteins from influenza A virus (IAV) are expressed in cells, ER stress is induced, resulting in rapid HA degradation via proteasomes...
October 18, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29045028/biological-effects-of-er-yag-laser-irradiation-on-the-proliferation-of-primary-human-gingival-fibroblasts
#18
Sophannary Kong, Akira Aoki, Kengo Iwasaki, Koji Mizutani, Sayaka Katagiri, Tomonari Suda, Shizuko Ichinose, Mayumi Ogita, Verica Pavlic, Yuichi Izumi
We investigated the biological effects of Er:YAG laser (2,940-nm; DELight(®) , HOYA ConBio, USA) irradiation at fluences of 3.6, 4.2, 4.9, 6.3, 8.1, or 9.7 J cm(-2) at 20 or 30 Hz for 20 or 30 s on primary human gingival fibroblasts (HGFs). Irradiation at 6.3 J cm(-2) promoted maximal cell proliferation, determined by WST-8 assay and crystal violet staining, but was accompanied by lactate dehydrogenase release, on day 3 post-irradiation. Elevation of ATP level, Ki67 staining, and cyclin-A2 mRNA expression confirmed that Er:YAG affected the cell cycle and increased the number of proliferating cells...
October 17, 2017: Journal of Biophotonics
https://www.readbyqxmd.com/read/29043683/fluorescence-imaging-of-autophagy-mediated-er-to-vacuole-trafficking-in-plants
#19
Hadas Peled-Zehavi, Gad Galili
Macroautophagy (hereafter referred to as autophagy) is a conserved mechanism in eukaryotic cells that delivers unneeded cellular components for degradation in the lytic organelle. In plants, as in other eukaryotes, autophagy begins in the formation of cup-shaped double membranes that engulf cytosolic material. The double membrane closes to form autophagosomes that are then transported to the vacuole for degradation. Autophagy can function as a bulk nonselective process or as a selective process targeting specific proteins, protein aggregates, organelles, or other cellular components for degradation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29043680/analysis-of-protein-glycosylation-in-the-er
#20
Jennifer Schoberer, Yun-Ji Shin, Ulrike Vavra, Christiane Veit, Richard Strasser
Protein N-glycosylation is an essential posttranslational modification which is initiated in the endoplasmic reticulum. In plants, the N-glycans play a pivotal role for protein folding and quality control. Through the interaction of glycan processing and binding reactions mediated by ER-resident glycosidases and specific carbohydrate binding proteins, the N-glycans contribute to the adoption of a native protein conformation. Properly folded glycoproteins are released from these processes and allowed to continue their transit to the Golgi where further processing and maturation of N-glycans leads to the formation of more complex structures with different functions...
2018: Methods in Molecular Biology
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