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ER-associated degradation

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https://www.readbyqxmd.com/read/29330040/yod1-attenuates-neurogenic-proteotoxicity-through-its-deubiquitinating-activity
#1
Kunikazu Tanji, Fumiaki Mori, Yasuo Miki, Jun Utsumi, Hidenao Sasaki, Akiyoshi Kakita, Hitoshi Takahashi, Koichi Wakabayashi
Ubiquitination, a fundamental post-translational modification of intracellular proteins, is enzymatically reversed by deubiquitinase enzymes (deubiquitinases). >90 deubiquitinases have been identified. One of these enzymes, YOD1, possesses deubiquitinase activity and is similar to ovarian tumor domain-containing protein 1, which is associated with regulation of the endoplasmic reticulum (ER)-associated degradation pathway. Indeed, YOD1 is reported to be involved in the ER stress response induced by mislocalization of unfolded proteins in mammalian cells...
January 10, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29323465/multiplexed-digital-mrna-expression-analysis-profiles-system-wide-changes-in-mrna-abundance-and-responsiveness-of-upr-specific-gene-expression-changes-during-batch-culture-of-recombinant-chinese-hamster-ovary-cells
#2
Rodrigo Maldonado-Agurto, Alan J Dickson
The unfolded protein response (UPR) signalling pathway is viewed as critical for setting the effectiveness of recombinant protein expression in CHO cells. In this study, we used Nanostring nCounter technology to study expression of a group of genes associated with cellular processes linked to UPR activation under ER stress and the changing environment of a batch culture. Time course induction of ER stress, using tunicamycin (TM), showed a group of genes such as Chop, Trb3, Sqstm1, Grp78 and Herpud1 responded rapidly to TM inhibition of N-glycosylation, whilst others such as Atf5, Odz4 and Birc5 exhibited a delayed response...
January 11, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29322304/causative-genes-in-amyotrophic-lateral-sclerosis-and-protein-degradation-pathways-a-link-to-neurodegeneration
#3
REVIEW
C Maurel, A Dangoumau, S Marouillat, C Brulard, A Chami, R Hergesheimer, P Corcia, H Blasco, C R Andres, P Vourc'h
Amyotrophic lateral sclerosis (ALS) is a disease caused by the degeneration of motor neurons (MNs) leading to progressive muscle weakness and atrophy. Several molecular pathways have been implicated, such as glutamate-mediated excitotoxicity, defects in cytoskeletal dynamics and axonal transport, disruption of RNA metabolism, and impairments in proteostasis. ALS is associated with protein accumulation in the cytoplasm of cells undergoing neurodegeneration, which is a hallmark of the disease. In this review, we focus on mechanisms of proteostasis, particularly protein degradation, and discuss how they are related to the genetics of ALS...
January 10, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29316847/chloroquine-promotes-the-recovery-of-acute-spinal-cord-injury-by-inhibiting-autophagy-associated-inflammation-and-endoplasmic-reticulum-stress
#4
Fenzan Wu, Xiaojie Wei, Yanqing Wu, Xiaoxia Kong, Aiping Hu, Songlin Tong, Yanlong Liu, Fanhua Gong, Ling Xie, Jinjing Zhang, Jian Xiao, Hongyu Zhang
Spinal cord injury (SCI) is a severe nervous system disease that may lead to lifelong disability. Studies have shown that autophagy plays a key role in various diseases; however, the mechanisms regulating crosstalk between autophagy, inflammation and endoplasmic reticulum (ER) stress during SCI recovery remain unclear. This study was designed to investigate the mechanism by which chloroquine (CQ) inhibits autophagy-associated inflammation and ER-stress in rats during their recovery from acute SCI. We evaluated the locomotor function, level of autophagy, and levels of inflammatory cytokines and ER-stress associated proteins and examined the degradation of the key regulator of inflammation I-κBα through autophagy by analyzing the colocalization of I-κBα, p62 and LC3-II...
January 9, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29313416/dicot-specific-atg8-interacting-ati3-proteins-interact-with-conserved-ubac2-proteins-and-play-critical-roles-in-plant-stress-responses
#5
Jie Zhou, Zhe Wang, Xiaoting Wang, Xifeng Li, Zhenchao Zhang, Baofang Fan, Cheng Zhu, Zhixiang Chen
Selective macroautophagy/autophagy targets specific cargo by autophagy receptors through interaction with ATG8 (autophagy-related protein 8)/MAP1LC3 (microtubule associated protein 1 light chain 3) for degradation in the vacuole. Here, we report the identification and characterization of 3 related ATG8-interacting proteins (AT1G17780/ATI3A, AT2G16575/ATI3B and AT1G73130/ATI3C) from Arabidopsis. ATI3 proteins contain a WxxL LC3-interacting region (LIR) motif at the C terminus required for interaction with ATG8...
January 9, 2018: Autophagy
https://www.readbyqxmd.com/read/29311259/the-endosomal-trafficking-factors-corvet-and-escrt-suppress-plasma-membrane-residence-of-the-renal-outer-medullary-potassium-channel-romk
#6
Timothy D Mackie, Bo-Young Kim, Arohan R Subramanya, Daniel J Bain, Allyson F O'Donnell, Paul A Welling, Jeffrey L Brodsky
Protein trafficking can act as the primary regulatory mechanism for ion channels with high open probabilities, such as the renal outer medullary (ROMK) channel. ROMK, also known as Kir1.1 (KCNJ1), is the major route for potassium secretion into the pro-urine and plays an indispensable role in regulating serum potassium and urinary concentrations. However, the cellular machinery that regulates ROMK trafficking has not been fully defined. To identify regulators of the cell-surface population of ROMK, we expressed a pH-insensitive version of the channel in the budding yeast Saccharomyces cerevisiae...
January 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29310837/assessment-of-a-fbxw8-frameshift-mutation-c-1312_1313delgt-in-breast-cancer-patients-and-controls-from-central-europe
#7
Jing Wang, Natalia Bogdanova, Peter Schürmann, Tjoung-Won Park-Simon, Robert Geffers, Thilo Dörk
F-box proteins participate in multiple cellular processes through ubiquitylation and subsequent degradation of target proteins, such as cyclin D1 as target of FBXW8. To investigate the spectrum of FBXW8 germ-line mutations in patients with breast cancer and healthy controls, we analyzed the whole FBXW8 coding region and flanking untranslated portions in germ-line DNA samples of 91 breast cancer patients and 277 healthy controls using next-generation amplicon sequencing. Five missense variants, one splice site variant, one frameshift variant, one synonymous variant, and one variant in the 3'-UTR were identified...
January 2018: Cancer Genetics
https://www.readbyqxmd.com/read/29301955/the-cytokinin-oxidase-dehydrogenase-ckx1-is-a-membrane-bound-protein-requiring-homooligomerization-in-the-endoplasmic-reticulum-for-its-cellular-activity
#8
Michael C E Niemann, Henriette Weber, Tomáš Hluska, Georgeta Leonte, Samantha M Anderson, Ondrej Novak, Alessandro Senes, Tomas Werner
Degradation of the plant hormone cytokinin is controlled by cytokinin oxidase/dehydrogenase (CKX) enzymes. The molecular and cellular behavior of these proteins is still largely unknown. In this study, we show that CKX1 is a type-II single-pass membrane protein that predominantly localizes to the endoplasmic reticulum (ER). This indicates that this CKX isoform is a bona fide ER protein directly controlling the cytokinin which triggers the signaling from the ER. By using various approaches, we demonstrate that CKX1 forms homodimers and homooligomers in vivo...
January 4, 2018: Plant Physiology
https://www.readbyqxmd.com/read/29300766/sec16a-a-key-protein-in-copii-vesicle-formation-regulates-the-stability-and-localization-of-the-novel-ubiquitin-ligase-rnf183
#9
Yan Wu, Xiao Peng Guo, Soshi Kanemoto, Yujiro Maeoka, Atsushi Saito, Rie Asada, Koji Matsuhisa, Yosuke Ohtake, Kazunori Imaizumi, Masayuki Kaneko
We identified 37 ubiquitin ligases containing RING-finger and transmembrane domains. Of these, we found that RNF183 is abundantly expressed in the kidney. RNF183 predominantly localizes to the endoplasmic reticulum (ER), Golgi, and lysosome. We identified Sec16A, which is involved in coat protein complex II vesicle formation, as an RNF183-interacting protein. RNF183 colocalized with Sec16A and interacted through the central conserved domain (CCD) of Sec16A. Although Sec16A is not a substrate for RNF183, RNF183 was more rapidly degraded by the ER-associated degradation (ERAD) in the absence of Sec16A...
2018: PloS One
https://www.readbyqxmd.com/read/29295953/the-endoplasmic-reticulum-residing-chaperone-bip-is-short-lived-and-metabolized-through-n-terminal-arginylation
#10
Sang Mi Shim, Ha Rim Choi, Ki Woon Sung, Yoon Jee Lee, Sung Tae Kim, Daeho Kim, Su Ran Mun, Joonsung Hwang, Hyunjoo Cha-Molstad, Aaron Ciechanover, Bo Yeon Kim, Yong Tae Kwon
BiP and other endoplasmic reticulum (ER)-resident proteins are thought to be metabolically stable and to function primarily in the ER lumen. We sought to assess how the abundance of these proteins dynamically fluctuates in response to various stresses and how their subpopulations are relocated to non-ER compartments such as the cytosol. We showed that the molecular chaperone BiP (also known as GRP78) was short-lived under basal conditions and ER stress. The turnover of BiP was in part driven by its amino-terminal arginylation (Nt-arginylation) by the arginyltransferase ATE1, which generated an autophagic N-degron of the N-end rule pathway...
January 2, 2018: Science Signaling
https://www.readbyqxmd.com/read/29284678/the-cue1-domain-of-the-snf2-like-chromatin-remodeler-smarcad1-mediates-its-association-with-krab-associated-protein-1-kap1-and-kap1-target-genes
#11
Dong Ding, Philipp Bergmaier, Parysatis Sachs, Marius Klangwart, Tamina Rückert, Nora Bartels, Jeroen Demmers, Mike Dekker, Raymond A Poot, Jacqueline E Mermoud
Chromatin in embryonic stem cells (ESCs) differs markedly from that in somatic cells, with ESCs exhibiting a more open chromatin configuration. Accordingly, ATP-dependent chromatin remodeling complexes are important regulators of ESC homeostasis. Depletion of the remodeler SMARCAD1, an ATPase of the SNF2 family, has been shown to affect stem cell state, but the mechanistic explanation for this effect is unknown. Here, we set out to gain further insights into the function of SMARCAD1 in mouse ESCs. We identified KRAB-associated protein 1 (KAP1) as the stoichiometric binding partner of SMARCAD1 in ESCs...
December 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29277369/implication-of-altered-ubiquitin-proteasome-system-and-er-stress-in-the-muscle-atrophy-of-diabetic-rats
#12
S Sreenivasa Reddy, Karnam Shruthi, Y Konda Prabhakar, Gummadi Sailaja, G Bhanuprakash Reddy
BACKGROUND: Skeletal muscle is adversely affected in type-1 diabetes, and excessively stimulated ubiquitin-proteasome system (UPS) was found to be a leading cause of muscle wasting or atrophy. The role of endoplasmic reticulum (ER) stress in muscle atrophy of type-1 diabetes is not known. Hence, we investigated the role of UPS and ER stress in the muscle atrophy of chronic diabetes rat model. METHODS: Diabetes was induced with streptozotocin (STZ) in male Sprague-Dawley rats and were sacrificed 2- and 4-months thereafter to collect gastrocnemius muscle...
December 22, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29247078/high-capacity-of-the-endoplasmic-reticulum-to-prevent-secretion-and-aggregation-of-amyloidogenic-proteins
#13
Lisa Vincenz-Donnelly, Hauke Holthusen, Roman Körner, Erik C Hansen, Jenny Presto, Jan Johansson, Ritwick Sawarkar, F Ulrich Hartl, Mark S Hipp
Protein aggregation is associated with neurodegeneration and various other pathologies. How specific cellular environments modulate the aggregation of disease proteins is not well understood. Here, we investigated how the endoplasmic reticulum (ER) quality control system handles β-sheet proteins that were designed de novo to form amyloid-like fibrils. While these proteins undergo toxic aggregation in the cytosol, we find that targeting them to the ER (ER-β) strongly reduces their toxicity. ER-β is retained within the ER in a soluble, polymeric state, despite reaching very high concentrations exceeding those of ER-resident molecular chaperones...
December 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29246447/factor-vii-deficiency-unveiling-the-cellular-and-molecular-mechanisms-underlying-three-model-alterations-of-the-enzyme-catalytic-domain
#14
Maria Eugenia Chollet, Elisabeth Andersen, Ellen Skarpen, Christiane F Myklebust, Christian Koehler, Jens Preben Morth, Ampaiwan Chuansumrit, Mirko Pinotti, Francesco Bernardi, Bernd Thiede, Per Morten Sandset, Grethe Skretting
Activated factor (F) VII is a vitamin K-dependent glycoprotein that initiates blood coagulation upon interaction with tissue factor. FVII deficiency is the most common of the rare congenital bleeding disorders. While the mutational pattern has been extensively characterized, the pathogenic molecular mechanisms of mutations, particularly at the intracellular level, have been poorly defined. Here, we aimed at elucidating the mechanisms underlying altered FVII biosynthesis in the presence of three mutation types in the catalytic domain: a missense change, a microdeletion and a frameshift/elongation, associated with severe or moderate to severe phenotypes...
December 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29241549/trafficking-mediated-sting-degradation-requires-sorting-to-acidified-endolysosomes-and-can-be-targeted-to-enhance-anti-tumor-response
#15
Vijay K Gonugunta, Tomomi Sakai, Vladislav Pokatayev, Kun Yang, Jianjun Wu, Nicole Dobbs, Nan Yan
STING is an endoplasmic reticulum (ER)-associated transmembrane protein that turns on and quickly turns off downstream signaling as it translocates from the ER to vesicles. How STING signaling is attenuated during trafficking remains poorly understood. Here, we show that trafficking-mediated STING degradation requires ER exit and function of vacuolar ATPase complex. Late-stage STING vesicles are sorted to Rab7-positive endolysosomes for degradation. Based on analysis of existing structures, we also identified the helix amino acid 281 (aa281)-297 as a motif required for trafficking-mediated STING degradation...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29238611/structural-basis-for-nucleotide-modulated-p97-association-with-the-er-membrane
#16
Wai Kwan Tang, Ting Zhang, Yihong Ye, Di Xia
Association of the cytosolic AAA (ATPases associated with various cellular activities) protein p97 to membranes is essential for various cellular processes including endoplasmic reticulum (ER)-associated degradation. The p97 consists of two ATPase domains and an N domain that interacts with numerous cofactors. The N domain of p97 is known to undergo a large nucleotide-dependent conformation switch, but its physiological relevance is unclear. Here we show p97 is recruited to canine ER membranes predominantly by interacting with VCP-interacting membrane protein (VIMP), an ER-resident protein...
2017: Cell Discovery
https://www.readbyqxmd.com/read/29236390/serum-glycomarkers-of-endoplasmic-reticulum-and-lysosomal-endosomal-system-stress-in-human-healthy-aging-and-diseases
#17
I U Pismenetskaya, T D Butters
To verify the idea that extracellular free oligosaccharides might be able to reflect the functional status of the endoplasmic reticulum (ER) and lysosomal-endosomal system, HPLC-profiles of serum-derived free oligosaccharides (FOS) in human healthy aging, acute myeloproliferative neoplasms, and cardiovascular pathologies were compared with intracellular glycans. After plasma deproteinization and FOS purification the oligosaccharides were labelled with anthranilic acid, separated into the neutral and charged with QAE Sephadex (Q25-120) chromatography and analysed using high-performance liquid chromatography (HPLC)...
January 2017: Ukrainian Biochemical Journal
https://www.readbyqxmd.com/read/29233968/hrd1-prevents-apoptosis-in-renal-tubular-epithelial-cells-by-mediating-eif2%C3%AE-ubiquitylation-and-degradation
#18
Yujie Huang, Yifei Sun, Yizhi Cao, Hui Sun, Min Li, Hui You, Dongming Su, Yanjiao Li, Xiubin Liang
Apoptosis of renal tubular epithelial cells is a key feature of the pathogenicity associated with tubulointerstitial fibrosis and other kidney diseases. One factor that regulates important cellular processes like apoptosis and cell proliferation is HRD1, an E3 ubiquitin ligase that acts by promoting ubiquitylation and degradation of its target protein. However, the detailed mechanisms by which HRD1 acts as a regulator of apoptosis in renal tubular epithelial cells have not been established. In our previous liquid chromatography-tandem mass spectrometry (LC-MS/MS) study (Mol Endocrinol...
December 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29232193/testosterone-regulates-granzyme-k-expression-in-rat-testes
#19
Dibyendu Dutta, In Park, Hiwot Guililat, Samuel Sang, Arpita Talapatra, Barkha Singhal, Nathaniel C Mills
OBJECTIVE: Testosterone depletion induces increased germ cell apoptosis in testes. However, limited studies exist on genes that regulate the germ cell apoptosis. Granzymes (GZM) are serine proteases that induce apoptosis in various tissues. Multiple granzymes, including GZMA, GZMB and GZMN, are present in testes. Th us, we investigated which granzyme may be testosterone responsive and possibly may have a role in germ cell apoptosis aft er testosterone depletion. METHODS: Ethylene dimethane sulfonate (EDS), a toxicant that selectively ablates the Leydig cells, was injected into rats to withdraw the testosterone...
October 26, 2017: Endocrine Regulations
https://www.readbyqxmd.com/read/29230100/dl-3-n-butylphthalide-prevents-the-disruption-of-blood-spinal-cord-barrier-via-inhibiting-endoplasmic-reticulum-stress-following-spinal-cord-injury
#20
Binbin Zheng, Yulong Zhou, Hongyu Zhang, Guangyong Yang, Zhenghua Hong, Dandan Han, Qingqing Wang, Zili He, Yanlong Liu, Fenzan Wu, Xie Zhang, Songlin Tong, Huazi Xu, Jian Xiao
After spinal cord injury (SCI), the destruction of blood-spinal cord barrier (BSCB) is shown to accelerate gathering of noxious blood-derived components in the nervous system, leading to secondary neurodegenerative damages. SCI activates endoplasmic reticulum stress (ER stress), which is considered to evoke secondary damages of neurons and glia. Recent evidence indicates that Dl-3-n-butylphthalide (NBP) has the neuroprotective effect in ischaemic brain injury, but whether it has protective effects on SCI or not is largely unclear...
2017: International Journal of Biological Sciences
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