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ER-associated degradation

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https://www.readbyqxmd.com/read/28091582/androgen-mediated-regulation-of-endoplasmic-reticulum-associated-degradation-and-its-effects-on-prostate-cancer
#1
Yalcin Erzurumlu, Petek Ballar
The endoplasmic reticulum (ER) comprises thirty percent of the newly translated proteins in eukaryotic cells. The quality control mechanism within the ER distinguishes between properly and improperly folded proteins and ensures that unwanted proteins are retained in the ER and subsequently degraded through ER-associated degradation (ERAD). Besides cleaning of misfolded proteins ERAD is also important for physiological processes by regulating the abundance of normal proteins of the ER. Thus it is important to unreveal the regulation patterns of ERAD...
January 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077573/a-retrochaperone-function-for-cdc48-the-cdc48-complex-is-required-for-retrotranslocated-erad-m-substrate-solubility
#2
Sonya E Neal, Raymond Mak, Eric J Bennett, Randolph Hampton
A surprising feature of ER-associated degradation (ERAD) is the movement, or retrotranslocation, of ubiquitinated substrates from the ER lumen or membrane to the cytosol where they are degraded by the 26S proteasome. Multispanning ER membrane proteins, called ERAD-M substrates, are retrotranslocated to the cytosol as full-length intermediates during ERAD and we have investigated how they maintain solubility. Using an in vivo assay, we show that retrotranslocated ERAD-M substrates are moved to the cytoplasm as part of the normal ERAD pathway, where they are part of a solely proteinacious complex...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28075474/isomahanine-induces-endoplasmic-reticulum-stress-and-simultaneously-triggers-p38%C3%A2-mapk-mediated-apoptosis-and-autophagy-in-multidrug-resistant-human-oral-squamous-cell-carcinoma-cells
#3
Tanyarath Utaipan, Anan Athipornchai, Apichart Suksamrarn, Surasak Chunsrivirot, Warangkana Chunglok
Advanced oral squamous cell carcinoma (OSCC) is typically aggressive and closely correlated with disease recurrence and poor survival. Multidrug resistance (MDR) is the most critical problem leading to therapeutic failure. Investigation of novel anticancer candidates targeting multidrug-resistant OSCC cells may provide a basis for developing effective strategies for OSCC treatment. In the present study, we investigated the cytotoxic mechanism of a carbazole alkaloid, namely isomahanine, in a multidrug‑resistant OSCC cell line CLS-354/DX...
January 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28075453/mir-375-inhibits-cancer-stem-cell-phenotype-and-tamoxifen-resistance-by-degrading-hoxb3-in-human-er-positive-breast-cancer
#4
Hui Fu, Lei Fu, Chao Xie, Wen-Shu Zuo, Yan-Song Liu, Mei-Zhu Zheng, Jin-Ming Yu
Cancer stem cell (CSC) formation and epithelial-mesenchymal transition (EMT) are pivotal events in tumor cell invasion and metastasis. They have been shown to occur in resistance to tamoxifen. Moreover, microRNAs (miRNAs) have been associated with CSCs, EMT as well as tamoxifen resistance. Studying molecular mechanism of CSCs, EMT as well as tamoxifen resistance will help us to further understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we showed that miR-375 inhibits CSC traits in breast cancer MCF-7 cells...
January 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28067409/crosstalk-of-autophagy-and-apoptosis-involvement-of-the-dual-role-of-autophagy-under-er-stress
#5
REVIEW
Shuling Song, Jin Tan, Yuyang Miao, Mengmeng Li, Qiang Zhang
Endoplasmic reticulum (ER) stress is a common cellular stress response that is triggered by a variety of conditions that disturb cellular homeostasis, and induces cell apoptosis. Autophagy, an important and evolutionarily conserved mechanism for maintaining cellular homeostasis, is closely related to the apoptosis induced by ER stress. There are common upstream signaling pathways between autophagy and apoptosis induced by ER stress, including PERK/ATF4, IRE1α, ATF6 and Ca(2+) . Autophagy can not only block the induction of apoptosis by inhibiting the activation of apoptosis-associated caspase which could reduce cellular injury, but also help to induce apoptosis...
January 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28053229/atg9-regulates-autophagosome-progression-from-the-endoplasmic-reticulum-in-arabidopsis
#6
Xiaohong Zhuang, Kin Pan Chung, Yong Cui, Weili Lin, Caiji Gao, Byung-Ho Kang, Liwen Jiang
Autophagy is a conserved pathway for bulk degradation of cytoplasmic material by a double-membrane structure named the autophagosome. The initiation of autophagosome formation requires the recruitment of autophagy-related protein 9 (ATG9) vesicles to the preautophagosomal structure. However, the functional relationship between ATG9 vesicles and the phagophore is controversial in different systems, and the molecular function of ATG9 remains unknown in plants. Here, we demonstrate that ATG9 is essential for endoplasmic reticulum (ER)-derived autophagosome formation in plants...
January 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28035820/genetically-encodable-bacterial-flavin-transferase-for-fluorogenic-protein-modification-in-mammalian-cells
#7
Myeong-Gyun Kang, Jumi Park, Gianfranco Balboni, Mi Hee Lim, Changwook Lee, Hyun-Woo Rhee
A bacterial flavin transferase (ApbE) was recently employed for flavin mononucleotide (FMN) modification on the Na+-translocating NADH:quinone oxidoreductase C (NqrC) protein in the pathogenic gram-negative bacterium Vibrio cholerae. We employed this unique post-translational modification in mammalian cells and found that the FMN transfer reaction robustly occurred when NqrC and ApbE were genetically targeted in the cytosol of live mammalian cells. Moreover, NqrC expression in the endoplasmic reticulum (NqrC-ER) induced the retro-translocation of NqrC to the cytosol, leading to the proteasome-mediated ER-associated degradation of NqrC, which is considered to be an innate immunological response toward the bacterial protein...
December 30, 2016: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28028074/chaperone-driven-degradation-of-a-misfolded-proinsulin-mutant-in-parallel-with-restoration-of-wild-type-insulin-secretion
#8
Corey N Cunningham, Kaiyu He, Anoop Arunagiri, Adrienne W Paton, James C Paton, Peter Arvan, Billy Tsai
In heterozygous patients with a diabetic syndrome called Mutant INS-gene-induced Diabetes of Youth (MIDY), there is decreased insulin secretion when mutant proinsulin expression prevents wild type (WT) proinsulin from exiting the endoplasmic reticulum (ER), which is essential for insulin production. Our previous results revealed that mutant Akita proinsulin is triaged by ER-associated degradation (ERAD). We now find that the ER chaperone Grp170 participates in the degradation process by shifting Akita proinsulin from high molecular weight (MW) complexes towards smaller oligomeric species that are competent to undergo ERAD...
December 27, 2016: Diabetes
https://www.readbyqxmd.com/read/27992019/worse-prognosis-in-breast-cancer-patients-can-be-predicted-by-immunohistochemical-analysis-of-positive-mmp-2-and-negative-estrogen-and-progesterone-receptors
#9
Edneia A S Ramos, Camila T da Silva, Graciele C M Manica, Isabela T Pereira, Liliane M B Klassen, Enilze M S F Ribeiro, Iglenir J Cavalli, Karin Braun-Prado, Rubens S Lima, Cicero A Urban, Fabrício F Costa, Lucia de Noronha, Giseli Klassen
Introduction: Breast cancer is the most cause of death, and approximately 90% of these deaths are due to metastases. Matrix metalloproteinase-2 (MMP-2) gelatinase activity is able to degrade a major constituent of the tumor microenvironment, type IV collagen. Two well-established proteins used as markers in clinical practice for breast cancer are the receptors for estrogen (ER) and progesterone (PR). Although the presence of these receptors has been associated with a better prognosis, loss of these proteins can occur during tumor progression, with subsequent resistance to hormone therapy...
November 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27991487/the-non-canonical-mitochondrial-inner-membrane-presequence-translocase-of-trypanosomatids-contains-two-essential-rhomboid-like-proteins
#10
Anke Harsman, Silke Oeljeklaus, Christoph Wenger, Jonathan L Huot, Bettina Warscheid, André Schneider
Mitochondrial protein import is essential for all eukaryotes. Here we show that the early diverging eukaryote Trypanosoma brucei has a non-canonical inner membrane (IM) protein translocation machinery. Besides TbTim17, the single member of the Tim17/22/23 family in trypanosomes, the presequence translocase contains nine subunits that co-purify in reciprocal immunoprecipitations and with a presequence-containing substrate that is trapped in the translocation channel. Two of the newly discovered subunits are rhomboid-like proteins, which are essential for growth and mitochondrial protein import...
December 19, 2016: Nature Communications
https://www.readbyqxmd.com/read/27973418/varicella-zoster-virus-infectious-cycle-er-stress-autophagic-flux-and-amphisome-mediated-trafficking
#11
REVIEW
Charles Grose, Erin M Buckingham, John E Carpenter, Jeremy P Kunkel
Varicella-zoster virus (VZV) induces abundant autophagy. Of the nine human herpesviruses, the VZV genome is the smallest (~124 kbp), lacking any known inhibitors of autophagy, such as the herpes simplex virus ICP34.5 neurovirulence gene. Therefore, this review assesses the evidence for VZV-induced cellular stress, endoplasmic-reticulum-associated degradation (ERAD), and autophagic flux during the VZV infectious cycle. Even though VZV is difficult to propagate in cell culture, the biosynthesis of the both N- and O-linked viral glycoproteins was found to be abundant...
December 10, 2016: Pathogens
https://www.readbyqxmd.com/read/27939849/a-squalene-synthase-protein-degradation-method-for-improved-sesquiterpene-production-in-saccharomyces-cerevisiae
#12
Bingyin Peng, Manuel R Plan, Panagiotis Chrysanthopoulos, Mark P Hodson, Lars K Nielsen, Claudia E Vickers
Sesquiterpenes are C15 isoprenoids with utility as fragrances, flavours, pharmaceuticals, and potential biofuels. Microbial fermentation is being examined as a competitive approach for bulk production of these compounds. Competition for carbon allocation between synthesis of endogenous sterols and production of the introduced sesquiterpene limits yields. Achieving balance between endogenous sterols and heterologous sesquiterpenes is therefore required to achieve economical yields. In the current study, the yeast Saccharomyces cerevisiae was used to produce the acyclic sesquiterpene alcohol, trans-nerolidol...
January 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/27935997/endoplasmic-reticulum-targeted-subunit-toxins-provide-a-new-approach-to-rescue-misfolded-mutant-proteins-and-revert-cell-models-of-genetic-diseases
#13
Humaira Adnan, Zhenbo Zhang, Hyun-Joo Park, Chetankumar Tailor, Clare Che, Mustafa Kamani, George Spitalny, Beth Binnington, Clifford Lingwood
Many germ line diseases stem from a relatively minor disturbance in mutant protein endoplasmic reticulum (ER) 3D assembly. Chaperones are recruited which, on failure to correct folding, sort the mutant for retrotranslocation and cytosolic proteasomal degradation (ER-associated degradation-ERAD), to initiate/exacerbate deficiency-disease symptoms. Several bacterial (and plant) subunit toxins, retrograde transport to the ER after initial cell surface receptor binding/internalization. The A subunit has evolved to mimic a misfolded protein and hijack the ERAD membrane translocon (dislocon), to effect cytosolic access and cytopathology...
2016: PloS One
https://www.readbyqxmd.com/read/27932072/a-case-for-sec61-channel-involvement-in-erad
#14
REVIEW
Karin Römisch
Proteins that misfold in the endoplasmic reticulum (ER) need to be transported back to the cytosol for degradation by proteasomes, a process known as ER-associated degradation (ERAD). The first candidate discussed as a retrograde protein transport conduit was the Sec61 channel which is responsible for secretory protein transport into the ER during biogenesis. The Sec61 channel binds the proteasome 19S regulatory particle which can extract an ERAD substrate from the ER. Nevertheless its role as a general export channel has been dismissed, and Hrd1 and Der1 have been proposed as alternatives...
December 5, 2016: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/27928013/herpes-simplex-virus-1-ul41-protein-suppresses-the-ire1-xbp1-signal-pathway-of-the-unfolded-protein-response-via-its-rnase-activity
#15
Pengchao Zhang, Chenhe Su, Zhangtao Jiang, Chunfu Zheng
: During viral infection, accumulation of viral proteins can cause stress in the endoplasmic reticulum (ER) and trigger the unfolded protein response (UPR) to restore the ER homeostasis. Inositol-requiring enzyme 1 (IRE1)-dependent pathway is the most conserved one of the three UPR signal pathways. Upon activation, IRE1 splices out an intron from the unspliced inactive form X-box binding protein 1 (XBP1(u)) mRNA and produces a transcriptionally potent spliced form (XBP1(s)). Previous studies have reported that the IRE1/XBP1 pathway is inhibited upon herpes simplex virus 1 (HSV-1) infection, however, the underlying molecular mechanism is still illusive...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27922637/a-human-carboxypeptidase-e-nf-%C3%AE-1-gene-mutation-in-an-alzheimer-s-disease-patient-leads-to-dementia-and-depression-in-mice
#16
Y Cheng, N X Cawley, T Yanik, S R K Murthy, C Liu, F Kasikci, D Abebe, Y P Loh
Patients with Alzheimer's disease (AD), a common dementia among the aging population, often also suffer from depression. This comorbidity is poorly understood. Although most forms of AD are not genetically inherited, we have identified a new human mutation in the carboxypeptidase E (CPE)/neurotrophic factor-α1 (NF-α1) gene from an AD patient that caused memory deficit and depressive-like behavior in transgenic mice. This mutation consists of three adenosine inserts, introducing nine amino acids, including two glutamines into the mutant protein, herein called CPE-QQ...
December 6, 2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27920251/a-homeostatic-shift-facilitates-endoplasmic-reticulum-proteostasis-through-transcriptional-integration-of-proteostatic-stress-response-pathways
#17
Liam Baird, Tadayuki Tsujita, Eri Kobayashi, Ryo Funayama, Takeshi Nagashima, Keiko Nakayama, Masayuki Yamamoto
Eukaryotic cells maintain protein homeostasis through the activity of multiple basal and inducible systems, which function in concert to allow cells to adapt to a wide range of environmental conditions. Whilst the transcriptional programs regulating individual pathways have been studied in detail, it is not known how the different pathways are transcriptionally integrated such that a deficiency in one pathway can be compensated by a change in an auxiliary response. One such pathway that plays an essential role in many proteostasis responses is the ubiquitin-proteasome system (UPS), which functions to degrade damaged, unfolded or short half-life proteins...
December 5, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27903760/interactions-between-intersubunit-transmembrane-domains-regulate-the-chaperone-dependent-degradation-of-an-oligomeric-membrane-protein
#18
Teresa M Buck, Alexa S Jordahl, Megan E Yates, Mike Preston, Emily Cook, Thomas R Kleyman, Jeffrey L Brodsky
The Epithelial Sodium Channel (ENaC) in kidney regulates blood pressure through control of sodium and volume homeostasis, and in lung ENaC regulates the volume of airway and alveolar fluids.  ENaC is a heterotrimer of homologous α-, β-, and γ-subunits, and assembles in the Endoplasmic Reticulum (ER) before it traffics and functions at the plasma membrane. Improperly folded or orphaned ENaC subunits are subject to ER quality control and targeted for ER associated degradation (ERAD). We previously established that a conserved, ER lumenal, molecular chaperone, Lhs1/GRP170, selects αENaC, but not β- or γENaC, for degradation when the ENaC subunits were individually expressed...
November 30, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27895152/spatio-temporal-uncoupling-of-mirna-mediated-translational-repression-and-target-rna-degradation-controls-mirnp-recycling-in-mammalian-cells
#19
Mainak Bose, Bahnisikha Barman, Avijit Goswami, Suvendra N Bhattacharyya
miRNA-mediated repression control expression of more than half of protein coding genes in metazoan animals. Translation repression is associated with target mRNA degradation initiated by decapping and deadenylation of the repressed mRNAs. Earlier evidence suggest Endoplasmic Reticulum (ER) as the site where miRNPs interact with their targets before the translation repression sets in but the subcellular location of subsequent degradation of miRNA-repressed messages is largely unidentified. Here, we explore the subcellular distribution of essential components of degradation machineries of miRNA-targeted mRNAs...
November 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27881664/lipid-disequilibrium-disrupts-er-proteostasis-by-impairing-erad-substrate-glycan-trimming-and-dislocation
#20
Milton To, Clark W H Peterson, Melissa A Roberts, Jessica L Counihan, Tiffany T Wu, Mercedes S Forster, Daniel K Nomura, James A Olzmann
The endoplasmic reticulum (ER) mediates the folding, maturation, and deployment of the secretory proteome. Proteins that fail to achieve their native conformation are retained in the ER and targeted for clearance by ER-associated degradation (ERAD), a sophisticated process that mediates the ubiquitin-dependent delivery of substrates to the 26S proteasome for proteolysis. Recent findings indicate that inhibition of long-chain acyl-CoA synthetases with triacsin C, a fatty acid analog, impairs lipid droplet (LD) biogenesis and ERAD, suggesting a role for LDs in ERAD...
November 23, 2016: Molecular Biology of the Cell
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