keyword
MENU ▼
Read by QxMD icon Read
search

ER-associated degradation

keyword
https://www.readbyqxmd.com/read/28808322/neuroinflammation-alters-cellular-proteostasis-by-producing-endoplasmic-reticulum-stress-autophagy-activation-and-disrupting-erad-activation
#1
Cristina Pintado, Sandra Macías, Helena Domínguez-Martín, Angélica Castaño, Diego Ruano
Proteostasis alteration and neuroinflammation are typical features of normal aging. We have previously shown that neuroinflammation alters cellular proteostasis through immunoproteasome induction, leading to a transient decrease of proteasome activity. Here, we further investigated the role of acute lipopolysaccharide (LPS)-induced hippocampal neuroinflammation in cellular proteostasis. In particular, we focused on macroautophagy (hereinafter called autophagy) and endoplasmic reticulum-associated protein degradation (ERAD)...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28782635/withaferin-a-induced-impaired-autophagy-and-unfolded-protein-response-in-human-breast-cancer-cell-lines-mcf-7-and-mda-mb-231
#2
Kamalini Ghosh, Soumasree De, Srimoyee Mukherjee, Sayantani Das, Amar Nath Ghosh, Sumita Bandyopadhyay Sengupta
The autophagy-lysosome pathway and the ubiquitin-proteasome systems are the two major routes for eukaryotic intracellular protein clearance. Cancerous cells often display elevated protein synthesis and byproduct disposal, thus, inhibition of the protein degradation pathways became an emerging approach for cancer therapy. The present study revealed that withaferin-A (WA), the biologically active withanolide derived from Withania somnifera, initially induced formation of autophagosomes in human breast cancer cell-lines, MCF-7 and MDA-MB-231...
August 3, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28777470/crosstalk-of-er-stress-mediated-autophagy-and-er-phagy-involvement-of-upr-and-the-core-autophagy-machinery
#3
REVIEW
Shuling Song, Jin Tan, Yuyang Miao, Qiang Zhang
Endoplasmic reticulum (ER) stress, a common cellular stress response, is closely related to the activation of autophagy that is an important and evolutionarily conserved mechanism for maintaining cellular homeostasis. Autophagy induced by ER stress mainly includes the ER stress-mediated autophagy and ER-phagy. The ER stress-mediated autophagy is characterized by the generation of autophagosomes that include worn-out proteins, protein aggregates, and damaged organelles. While the autophagosomes of ER-phagy selectively include ER membranes, and the double membranes also derive, at least in part, from the ER...
August 4, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28770435/implication-of-endoplasmic-reticulum-stress-in-autism-spectrum-disorder
#4
Koichi Kawada, Seisuke Mimori
Autism spectrum disorder (ASD) is categorized as a neurodevelopmental disorder according to the Diagnostic and Statistical Manual of Disorders, Fifth Edition and is defined as a congenital impairment of the central nervous system. ASD may be caused by a chromosomal abnormality or gene mutation. However, these etiologies are insufficient to account for the pathogenesis of ASD. Therefore, we propose that the etiology and pathogenesis of ASD are related to the stress of the endoplasmic reticulum (ER). ER stress, induced by valproic acid, increased in ASD mouse model, characterized by an unfolded protein response that is activated by this stress...
August 2, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28768697/a-novel-high-throughput-yeast-genetic-screen-for-factors-modifying-protein-levels-of-the-early-onset-torsion-dystonia-associated-variant-torsina%C3%AE-e
#5
Lucía F Zacchi, John C Dittmar, Michael J Mihalevic, Annette M Shewan, Benjamin L Schulz, Jeffrey L Brodsky, Kara A Bernstein
Dystonia is the third most common movement disorder, but its diagnosis and treatment remain challenging. One of the most severe types of Dystonia is Early-Onset Torsion Dystonia (EOTD). The best studied and validated EOTD-associated mutation, torsinAΔE, is a deletion of a C-terminal glutamate residue in the AAA+ ATPase, torsinA. TorsinA appears to be an Endoplasmic Reticulum (ER)/Nuclear Envelope chaperone with multiple roles in the secretory pathway and in determining subcellular architecture. Many functions are disabled in the torsinAΔE variant, and torsinAΔE is also less stable than wild-type torsinA and is a substrate for ER-associated degradation...
August 2, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28767417/a-novel-deubiquitinase-inhibitor-b-ap15-triggers-apoptosis-in-both-androgen-receptor-dependent-and-independent-prostate-cancers
#6
Jianyu Cai, Xiaohong Xia, Yuning Liao, Ningning Liu, Zhiqiang Guo, Jinghong Chen, Li Yang, Huidan Long, Qianqian Yang, Xiaolan Zhang, Lu Xiao, Xuejun Wang, Hongbiao Huang, Jinbao Liu
Prostate cancer (PCa) remains a leading cause of cancer-related death in men. Especially, a subset of patients will eventually progress to the metastatic castrate-resistant prostate cancer (CRPC) which is currently incurable. Deubiquitinases (DUBs) associated with the 19S proteasome regulatory particle are increasingly emerging as significant therapeutic targets in numerous cancers. Recently, a novel small molecule b-AP15 is identified as an inhibitor of the USP14/UCHL5 (DUBs) of the 19S proteasome, resulting in cell growth inhibition and apoptosis in several human cancer cell lines...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28743740/multiple-e2-ubiquitin-conjugating-enzymes-regulate-human-cytomegalovirus-us2-mediated-immunoreceptor-downregulation
#7
Michael L van de Weijer, Anouk B C Schuren, Dick J H van den Boomen, Arend Mulder, Frans H J Claas, Paul J Lehner, Robert Jan Lebbink, Emmanuel J H J Wiertz
Misfolded ER proteins are dislocated towards the cytosol and degraded by the ubiquitin-proteasome system in a process called ER-associated protein degradation (ERAD). During infection with human cytomegalovirus (HCMV), the viral US2 protein targets HLA class I molecules (HLA-I) for degradation via ERAD to avoid elimination by the immune system. US2-mediated degradation of HLA-I serves as a paradigm of ERAD and has facilitated the identification of TRC8 as an E3 ubiquitin ligase. To date, no specific E2 enzymes had been described for cooperation with TRC8...
July 25, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28740555/atg9b-deficiency-suppresses-autophagy-and-potentiates-endoplasmic-reticulum-stress-associated-hepatocyte-apoptosis-in-hepatocarcinogenesis
#8
Ning Wang, Hor-Yue Tan, Sha Li, Yibin Feng
The aim of this study was to investigate the mechanism underlying autophagy deficiency during hepatic carcinogenesis. For this purpose, we used choline-deficient, amino acid-defined (CDAA) hepatocarcinogenesis model in mice. miRNA microarrays combined with computational target predictions and GO analysis were used to identify molecular processes involved in carcinogenesis. PCR profiler array was employed to detect the dysregulated autophagy-related genes during carcinogenesis. We observed induction of hepatic tumours with increased inflammation, DNA damage, and cell death...
2017: Theranostics
https://www.readbyqxmd.com/read/28700330/translocation-of-heme-oxygenase-1-contributes-to-imatinib-resistance-in-chronic-myelogenous-leukemia
#9
Bianca Schaefer, Soenke Behrends
Heme oxygenase-1 (HO-1) degrades heme to bilirubin. In addition, it is upregulated in malignant disease and has been described as an important factor for cancer prognosis and therapy. Under physiological conditions HO-1 is anchored to the endoplasmic reticulum (ER). Under stress conditions HO-1 can be cleaved and subsequently translocates to the cytosol and nucleus.In this study we systematically investigated the influence of HO-1's catabolic activity and subcellular localization on resistance against the tyrosine kinase inhibitor imatinib in leukemia cells by confocal laser scanning microscopy, hemoglobin synthesis experiments and cell viability assays...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28693924/site-1-protease-and-lysosomal-homeostasis
#10
REVIEW
Renata Voltolini Velho, Raffaella De Pace, Sarah Klünder, Giorgia Di Lorenzo, Michaela Schweizer, Thomas Braulke, Sandra Pohl
The Golgi-resident site-1 protease (S1P) is a key regulator of cholesterol homeostasis and ER stress responses by converting latent transcription factors sterol regulatory element binding proteins (SREPBs) and activating transcription factor 6 (ATF6), as well as viral glycoproteins to their active forms. S1P is also essential for lysosome biogenesis by the proteolytic activation of the hexameric GlcNAc-1-phosphotransferase complex required for modification of newly synthesized lysosomal enzymes with the lysosomal targeting signal, mannose 6-phosphate...
July 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28690762/sestrin2-as-a-novel-biomarker-and-therapeutic-target-for-various-diseases
#11
REVIEW
Mazhar Pasha, Ali H Eid, Assaad A Eid, Yves Gorin, Shankar Munusamy
Sestrin2 (SESN2), a highly conserved stress-inducible metabolic protein, is known to repress reactive oxygen species (ROS) and provide cytoprotection against various noxious stimuli including genotoxic and oxidative stress, endoplasmic reticulum (ER) stress, and hypoxia. Studies demonstrate that the upregulation of Sestrin2 under conditions of oxidative stress augments autophagy-directed degradation of Kelch-like ECH-associated protein 1 (Keap1), which targets and breaks down nuclear erythroid-related factor 2 (Nrf2), a key regulator of various antioxidant genes...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28688841/how-mr1-presents-a-pathogen-metabolic-signature-to-mucosal-associated-invariant-t-mait-cells
#12
REVIEW
Hamish E G McWilliam, Jose A Villadangos
Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes restricted by the antigen (Ag)-presenting molecule MHC class I (MHC I)-related protein 1 (MR1). The Ags presented by MR1 are vitamin B-related Ags (VitBAgs), 'building-block' metabolites of riboflavin that are synthesized by a range of microbes. MR1 presentation is thus a unique mechanism for the immune detection of a pathogen metabolic signature. While the full picture of how MR1 accomplishes this remains incomplete, recent data show that, unlike other MHC molecules, MR1 operates by a presentation-on-demand mechanism...
July 5, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28682307/cryo-em-structure-of-the-protein-conducting-erad-channel-hrd1-in-complex-with-hrd3
#13
Stefan Schoebel, Wei Mi, Alexander Stein, Sergey Ovchinnikov, Ryan Pavlovicz, Frank DiMaio, David Baker, Melissa G Chambers, Huayou Su, Dongsheng Li, Tom A Rapoport, Maofu Liao
Misfolded endoplasmic reticulum (ER) proteins are retro-translocated through the membrane into the cytosol, where they are poly-ubiquitinated, extracted from the ER membrane, and degraded by the proteasome(1-4), a pathway termed ER-associated protein degradation (ERAD). Proteins with misfolded domains in the ER lumen or membrane are discarded through the ERAD-L and -M pathways, respectively. In S. cerevisiae, both pathways require the ubiquitin ligase Hrd1, a multi-spanning membrane protein with a cytosolic RING finger domain(5,6)...
July 6, 2017: Nature
https://www.readbyqxmd.com/read/28679634/sec61-blockade-by-mycolactone-inhibits-antigen-cross-presentation-independently-of-endosome-to-cytosol-export
#14
Jeff E Grotzke, Patrycja Kozik, Jean-David Morel, Francis Impens, Natalia Pietrosemoli, Peter Cresswell, Sebastian Amigorena, Caroline Demangel
Although antigen cross-presentation in dendritic cells (DCs) is critical to the initiation of most cytotoxic immune responses, the intracellular mechanisms and traffic pathways involved are still unclear. One of the most critical steps in this process, the export of internalized antigen to the cytosol, has been suggested to be mediated by Sec61. Sec61 is the channel that translocates signal peptide-bearing nascent polypeptides into the endoplasmic reticulum (ER), and it was also proposed to mediate protein retrotranslocation during ER-associated degradation (a process called ERAD)...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28669563/proteasomal-degradation-of-t-gondii-rop18-requires-derlin2
#15
Yuewen Tang, Meijuan Zheng, Ran An, Lijian Chen, Lingli Gong, Haijian Cai, Kang Liu, Li Yu, Jilong Shen, Jian Du
T. gondii is an obligate intracellular parasite, belonging to the Phylum Apicomplexa, infecting all warm-blooded animals including humans. During host cell invasion, specialized cytoskeletal and secretory organelles play a pivotal role. ROP18, as a member of the ROP2 family, has been identified as a key virulence factor mediating pathogenesis in T. gondii. Here, we identify an ER-resident protein, Derlin2, a factor implicated in the removal of misfolded proteins from the ER for cytosolic degradation, as a component of the machinery required for ER-associated protein degradation (ERAD)...
June 29, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28661051/n-linked-glycosylation-of-a-subunit-isoforms-is-critical-for-vertebrate-vacuolar-h-atpase-v-atpase-biosynthesis
#16
Sally Esmail, Norbert Kartner, Yeqi Yao, Joo Wan Kim, Reinhart A F Reithmeier, Morris F Manolson
The a subunit of the V0 membrane-integrated sector of human V-ATPase has four isoforms, a1-a4, with diverse and crucial functions in health and disease. They are encoded by four conserved paralogous genes, and their vertebrate orthologs have positionally conserved N-glycosylation sequons within the second extracellular loop, EL2, of the a subunit membrane domain. Previously, we have shown directly that the predicted sequon for the a4 isoform is indeed N-glycosylated. Here we extend our investigation to the other isoforms by transiently transfecting HEK 293 cells to express cDNA constructs of epitope-tagged human a1-a3 subunits, with or without mutations that convert Asn to Gln at putative N-glycosylation sites...
June 29, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28633019/edem-function-in-erad-protects-against-chronic-er-proteinopathy-and-age-related-physiological-decline-in-drosophila
#17
Michiko Sekiya, Akiko Maruko-Otake, Stephen Hearn, Yasufumi Sakakibara, Naoki Fujisaki, Emiko Suzuki, Kanae Ando, Koichi M Iijima
The unfolded protein response (UPR), which protects cells against accumulation of misfolded proteins in the ER, is induced in several age-associated degenerative diseases. However, sustained UPR activation has negative effects on cellular functions and may worsen disease symptoms. It remains unknown whether and how UPR components can be utilized to counteract chronic ER proteinopathies. We found that promotion of ER-associated degradation (ERAD) through upregulation of ERAD-enhancing α-mannosidase-like proteins (EDEMs) protected against chronic ER proteinopathy without inducing toxicity in a Drosophila model...
June 19, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28630040/endoplasmic-reticulum-associated-degradation-of-the-renal-potassium-channel-romk-leads-to-type-ii-bartter-syndrome
#18
Brighid M O'Donnell, Timothy D Mackie, Arohan R Subramanya, Jeffrey L Brodsky
Type II Bartter syndrome is caused by mutations in the renal outer medullary potassium (ROMK) channel, but the molecular mechanisms underlying this disease are poorly defined. To rapidly screen for ROMK function, we developed a yeast expression system and discovered that yeast cells lacking endogenous potassium channels could be rescued by WT ROMK but not by ROMK proteins containing any one of four Bartter mutations. We also found that the mutant proteins were significantly less stable than WT ROMK. However, their degradation was slowed in the presence of a proteasome inhibitor or when yeast cells contained mutations in the CDC48 or SSA1 gene, which is required for endoplasmic reticulum (ER)-associated degradation (ERAD)...
August 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28622300/the-als-linked-e102q-mutation-in-sigma-receptor-1-leads-to-er-stress-mediated-defects-in-protein-homeostasis-and-dysregulation-of-rna-binding-proteins
#19
Alice Dreser, Jan Tilmann Vollrath, Antonio Sechi, Sonja Johann, Andreas Roos, Alfred Yamoah, Istvan Katona, Saeed Bohlega, Dominik Wiemuth, Yuemin Tian, Axel Schmidt, Jörg Vervoorts, Marc Dohmen, Cordian Beyer, Jasper Anink, Eleonora Aronica, Dirk Troost, Joachim Weis, Anand Goswami
Amyotrophic lateral sclerosis (ALS) is characterized by the selective degeneration of motor neurons (MNs) and their target muscles. Misfolded proteins which often form intracellular aggregates are a pathological hallmark of ALS. Disruption of the functional interplay between protein degradation (ubiquitin proteasome system and autophagy) and RNA-binding protein homeostasis has recently been suggested as an integrated model that merges several ALS-associated proteins into a common pathophysiological pathway...
June 16, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28611990/structure-and-function-of-p97-and-pex1-6-type-ii-aaa-complexes
#20
REVIEW
Paul Saffert, Cordula Enenkel, Petra Wendler
Protein complexes of the Type II AAA+ (ATPases associated with diverse cellular activities) family are typically hexamers of 80-150 kDa protomers that harbor two AAA+ ATPase domains. They form double ring assemblies flanked by associated domains, which can be N-terminal, intercalated or C-terminal to the ATPase domains. Most prominent members of this family include NSF (N-ethyl-maleimide sensitive factor), p97/VCP (valosin-containing protein), the Pex1/Pex6 complex and Hsp104 in eukaryotes and ClpB in bacteria...
2017: Frontiers in Molecular Biosciences
keyword
keyword
121174
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"