keyword
MENU ▼
Read by QxMD icon Read
search

unfolded protein response

keyword
https://www.readbyqxmd.com/read/28926611/activation-of-the-unfolded-protein-response-in-sarcoma-cells-treated-with-rapamycin-or-temsirolimus
#1
Joseph W Briggs, Ling Ren, Kristi R Chakrabarti, Yien Che Tsai, Allan M Weissman, Ryan J Hansen, Daniel L Gustafson, Yousuf A Khan, Jonathan D Dinman, Chand Khanna
Activation of the unfolded protein response (UPR) in eukaryotic cells represents an evolutionarily conserved response to physiological stress. Here, we report that the mTOR inhibitors rapamycin (sirolimus) and structurally related temsirolimus are capable of inducing UPR in sarcoma cells. However, this effect appears to be distinct from the classical role for these drugs as mTOR inhibitors. Instead, we detected these compounds to be associated with ribosomes isolated from treated cells. Specifically, temsirolimus treatment resulted in protection from chemical modification of several rRNA residues previously shown to bind rapamycin in prokaryotic cells...
2017: PloS One
https://www.readbyqxmd.com/read/28925976/shiga-toxin-therapeutics-beyond-neutralization
#2
REVIEW
Gregory Hall, Shinichiro Kurosawa, Deborah J Stearns-Kurosawa
Ribotoxic Shiga toxins are the primary cause of hemolytic uremic syndrome (HUS) in patients infected with Shiga toxin-producing enterohemorrhagic Escherichia coli (STEC), a pathogen class responsible for epidemic outbreaks of gastrointestinal disease around the globe. HUS is a leading cause of pediatric renal failure in otherwise healthy children, resulting in a mortality rate of 10% and a chronic morbidity rate near 25%. There are currently no available therapeutics to prevent or treat HUS in STEC patients despite decades of work elucidating the mechanisms of Shiga toxicity in sensitive cells...
September 19, 2017: Toxins
https://www.readbyqxmd.com/read/28924219/mesoscopic-model-for-dna-g-quadruplex-unfolding
#3
A E Bergues-Pupo, I Gutiérrez, J R Arias-Gonzalez, F Falo, A Fiasconaro
Genomes contain rare guanine-rich sequences capable of assembling into four-stranded helical structures, termed G-quadruplexes, with potential roles in gene regulation and chromosome stability. Their mechanical unfolding has only been reported to date by all-atom simulations, which cannot dissect the major physical interactions responsible for their cohesion. Here, we propose a mesoscopic model to describe both the mechanical and thermal stability of DNA G-quadruplexes, where each nucleotide of the structure, as well as each central cation located at the inner channel, is mapped onto a single bead...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924165/manf-regulates-hypothalamic-control-of-food-intake-and-body-weight
#4
Su Yang, Huiming Yang, Renbao Chang, Peng Yin, Yang Yang, Weili Yang, Shanshan Huang, Marta A Gaertig, Shihua Li, Xiao-Jiang Li
The hypothalamus has a vital role in controlling food intake and energy homeostasis; its activity is modulated by neuropeptides and endocrine factors. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor that is also localized in the endoplasmic reticulum (ER) in neurons. Here we show that MANF is highly enriched in distinct nuclei of the mouse hypothalamus, and that MANF expression in the hypothalamus is upregulated in response to fasting. Increasing or decreasing hypothalamic MANF protein levels causes hyperphagia or hypophagia, respectively...
September 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28921568/neuronal-activity-dependent-local-activation-of-dendritic-unfolded-protein-response-promotes-expression-of-brain-derived-neurotrophic-factor-in-cell-soma
#5
Atsushi Saito, Longjie Cai, Koji Matsuhisa, Yosuke Ohtake, Masayuki Kaneko, Soshi Kanemoto, Rie Asada, Kazunori Imaizumi
Unfolded protein response (UPR) has roles not only in resolving the accumulation of unfolded proteins owing to endoplasmic reticulum (ER) stress, but also in regulation of cellular physiological functions. ER stress transducers providing the branches of UPR signaling are known to localize in distal dendritic ER of neurons. These reports suggest that local activation of UPR branches may produce integrated outputs for distant communication, and allow regulation of local events in highly polarized neurons. Here, we demonstrated that synaptic activity- and brain-derived neurotrophic factor (BDNF)-dependent local activation of UPR signaling could be associated with dendritic functions through retrograde signal propagation by using murine neuroblastoma cell line, Neuro-2A and primary cultured hippocampal neurons derived from postnatal day 0 litter C57BL/6 mice...
September 16, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28917667/amyloid-%C3%AE-42-clearance-and-neuroprotection-mediated-by-x-box-binding-protein-1-signaling-decline-with-aging-in-the-drosophila-brain
#6
María S Marcora, Lautaro F Belfiori-Carrasco, Nadia I Bocai, Laura Morelli, Eduardo M Castaño
The unfolded protein response (UPR) may be pathogenically related to Alzheimer's disease. Yet, the effects of chronic amyloid-β42 (Aβ42) accumulation and UPR activation upon neurotoxicity remain unclear. Here, we show that neuronal Aβ42 expression in Drosophila activated the inositol-requiring protein-1/X-box binding protein 1 (XBP1) UPR branch before the onset of behavioral impairment and persisted with aging. Early upregulation of hsc3/BiP, a target of XBP1 and activating transcription factor 6 pathways, was also sustained in old animals...
August 24, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28916625/transcriptional-correlates-of-memory-maintenance-following-long-term-sensitization-of-aplysia-californica
#7
Catherine Conte, Samantha Herdegen, Saman Kamal, Jency Patel, Ushma Patel, Leticia Perez, Marissa Rivota, Robert J Calin-Jageman, Irina E Calin-Jageman
We characterized the transcriptional response accompanying maintenance of long-term sensitization (LTS) memory in the pleural ganglia of Aplysia californica using microarray (N = 8) and qPCR (N = 11 additional samples). We found that 24 h after memory induction there is strong regulation of 1198 transcripts (748 up and 450 down) in a pattern that is almost completely distinct from what is observed during memory encoding (1 h after training). There is widespread up-regulation of transcripts related to all levels of protein production, from transcription (e...
October 2017: Learning & Memory
https://www.readbyqxmd.com/read/28916354/abnormal-sodium-channel-mrna-splicing-in-hypertrophic-cardiomyopathy
#8
Adam M Noyes, Anyu Zhou, Ge Gao, Lianzhi Gu, Sharlene Day, J Andrew Wasserstrom, Samuel C Dudley
BACKGROUND: Our previous studies showed that in ischemic and nonischemic heart failure (HF), the voltage-gated cardiac Na(+) channel α subunit (SCN5A) mRNA is abnormally spliced to produce two truncated transcript variants (E28C and D) that activate the unfolded protein response (UPR). We tested whether SCN5A post-transcriptional regulation was abnormal in hypertrophic cardiomyopathy (HCM). MATERIAL AND METHODS: Human heart tissue was obtained from HCM patients...
September 7, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28915629/ier3ip1-deficiency-leads-to-increased-%C3%AE-cell-death-and-decreased-%C3%AE-cell-proliferation
#9
Juan Sun, Decheng Ren
Mutations in the gene for Immediate Early Response 3 Interacting Protein 1 (IER3IP1) cause permanent neonatal diabetes mellitus in human. The mechanisms involved have not been determined and the role of IER3IP1 in β-cell survival has not been characterized. In order to determine if there is a molecular link between IER3IP1 deficiency and β-cell survival and proliferation, we knocked down Ier3ip1 gene expression in mouse MIN6 insulinoma cells. IER3IP1 suppression induced apoptotic cell death which was associated with an increase in Bim and a decrease in Bcl-xL...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915587/expression-and-release-of-glucose-regulated-protein-78-grp78-in-multiple-myeloma
#10
Normann Steiner, Bojana Borjan, Roman Hajek, Karin Jöhrer, Georg Göbel, Wolfgang Willenbacher, Johann Kern, Eberhard Gunsilius, Gerold Untergasser
INTRODUCTION: Multiple myeloma (MM) is a plasma cell neoplasm that is mostly incurable due to acquired resistance during the treatment course. Thus, we evaluated expression and release of glucose-regulated protein 78 kDa (GRP78/BiP), an endoplasmic reticulum (ER) based pro-survival chaperone involved in immunoglobulin folding and unfolded protein responses. RESULTS: GRP78 protein expression in the ER and on the cell surface did not significantly differ between MGUS, NDMM and RRMM patients although there was a trend to higher surface expression in RRMM...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913741/pressure-dependence-of-side-chain-13-c-chemical-shifts-in-model-peptides-ac-gly-gly-xxx-ala-nh2
#11
Markus Beck Erlach, Joerg Koehler, Edson Crusca, Claudia E Munte, Masatsune Kainosho, Werner Kremer, Hans Robert Kalbitzer
For evaluating the pressure responses of folded as well as intrinsically unfolded proteins detectable by NMR spectroscopy the availability of data from well-defined model systems is indispensable. In this work we report the pressure dependence of (13)C chemical shifts of the side chain atoms in the protected tetrapeptides Ac-Gly-Gly-Xxx-Ala-NH2 (Xxx, one of the 20 canonical amino acids). Contrary to expectation the chemical shifts of a number of nuclei have a nonlinear dependence on pressure in the range from 0...
September 14, 2017: Journal of Biomolecular NMR
https://www.readbyqxmd.com/read/28912266/lysine-trimethylation-regulates-78-kda-glucose-regulated-protein-proteostasis-during-endoplasmic-reticulum-stress
#12
Jonas Sieber, Nicolas Wieder, Mauricio Ostrosky-Frid, Moran Dvela-Levitt, Ozan Aygün, Namrata D Udeshi, Steven A Carr, Anna Greka
The upregulation of chaperones such as the 78-kDa glucose-regulated protein (GRP78; also referred to as BiP or HSPA5) is part of the adaptive cellular response to endoplasmic reticulum (ER) stress. GRP78 is widely used as a marker of the unfolded protein response, associated with sustained ER stress. Here, we report the discovery of a proteostatic mechanism involving GRP78 trimethylation in the context of ER stress. Using mass spectrometry-based proteomics, we identified two GRP78 fractions, one homeostatic and one induced by ER stress...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28904818/nf-%C3%AE%C2%BAb-pathway-link-with-er-stress-induced-autophagy-and-apoptosis-in-cervical-tumor-cells
#13
Xiaolan Zhu, Li Huang, Jie Gong, Chun Shi, Zhiming Wang, Bingkun Ye, Aiguo Xuan, Xiaosong He, Dahong Long, Xiao Zhu, Ningfang Ma, Shuilong Leng
Targeting endoplasmic reticulum (ER) stress is being investigated for its anticancer effect in various cancers, including cervical cancer. However, the molecular pathways whereby ER stress mediates cell death remain to be fully elucidated. In this study, we confirmed that ER stress triggered by compounds such as brefeldin A (BFA), tunicamycin (TM), and thapsigargin (TG) leads to the induction of the unfolded protein response (UPR) in cervical cancer cell lines, which is characterized by elevated levels of inositol-requiring kinase 1α, glucose-regulated protein-78, and C/EBP homologous protein, and swelling of the ER observed by transmission electron microscope (TEM)...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28904177/limited-proteolysis-as-a-tool-to-probe-the-tertiary-conformation-of-dysferlin-and-structural-consequences-of-patient-missense-variant-l344p
#14
Natalie Woolger, Adam Bournazos, Reece A Sophocleous, Frances J Evesson, Angela Lek, Birgit Driemer, R Bryan Sutton, Sandra T Cooper
Dysferlin is a large transmembrane protein that plays a key role in cell membrane repair, and underlies a recessive form of inherited muscular dystrophy. Dysferlinopathy is characterized by absence or marked reduction of dysferlin protein, with 43% of reported pathogenic variants being missense variants that span the length of the dysferlin protein. The unique structure of dysferlin, with seven tandem C2-domains separated by linkers, suggest dysferlin may dynamically associate with phospholipid membranes in response to Ca2+ signaling...
September 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28903548/role-of-the-unfolded-protein-response-in-the-development-of-central-nervous-system
#15
Naoya Murao, Hideki Nishitoh
The unfolded protein response (UPR) is an intracellular homeostatic signalling pathway that is induced by accumulated misfolded/unfolded proteins in the endoplasmic reticulum (ER). The UPR is closely associated with the development of disease in several tissues, including the central nervous system (CNS), in response to ER stress. More recently, the unique features and importance of the UPR have been revealed in neural stem cells (NSCs) and differentiated CNS cells [neurons and glial cells (astrocytes and oligodendrocytes)]...
September 1, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28901250/xbp-1-a-cellular-target-for-the-development-of-novel-anti-viral-strategies
#16
Han Kee Ong, Benjamin P C Soo, Kai Ling Chu, Sheng-Hao Chao
X-box binding protein 1 (XBP-1) is a key regulator of the unfolded protein response (UPR), which is activated in response to endoplasmic reticulum (ER) stress. Cells contain two protein isoforms of XBP-1, the active isoform (XBP-1S) and the inactive isoform (XBP-1U). Induction of UPR leads to the generation of XBP-1S while XBP-1U is dominant in ER stress-free cells. XBP-1S is a transcriptional activator and regulates the expression of a subset of UPR genes. Importantly, recent studies have demonstrated the essential role of XBP-1S in various human diseases, such as viral infections...
September 11, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28900910/the-stim-orai-pathway-conformational-coupling-between-stim-and-orai-in-the-activation-of-store-operated-ca-2-entry
#17
Robert M Nwokonko, Xiangyu Cai, Natalia A Loktionova, Youjun Wang, Yandong Zhou, Donald L Gill
Store-operated Ca(2+) entry fulfills a crucial role in controlling Ca(2+) signals in almost all cells. The Ca(2+)-sensing stromal interaction molecule (STIM) proteins in the endoplasmic reticulum (ER) undergo complex conformational changes in response to depleted ER luminal Ca(2+), allowing them to unfold and become trapped in ER-plasma membrane (PM) junctions. Dimers of STIM proteins trap and gate the plasma membrane Orai Ca(2+) channels within these junctions to generate discrete zones of high Ca(2+) and regulate sensitive Ca(2+)-dependent intracellular signaling pathways...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28900680/coordinating-organismal-metabolism-during-protein-misfolding-in-the-er-through-the-unfolded-protein-response
#18
Vishwanatha K Chandrahas, Jaeseok Han, Randal J Kaufman
The endoplasmic reticulum (ER) is a cellular organelle responsible for folding of secretory and membrane proteins. Perturbance in ER homeostasis caused by various intrinsic/extrinsic stimuli challenges the protein-folding capacity of the ER, leading to an ER dysfunction, called ER stress. Cells have developed a defensive response to adapt and/or survive in the face of ER stress that may be detrimental to cell function and survival. When exposed to ER stress, the cell activates a complex and elaborate signaling network that includes translational modulation and transcriptional induction of genes...
September 13, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28899199/transcriptional-regulation-by-nrf2
#19
Claudia Tonelli, Iok In Christine Chio, David A Tuveson
SIGNIFICANCE: Nrf2 is a transcription factor that coordinates the basal and stress-inducible activation of a vast array of cytoprotective genes. Understanding the regulation of Nrf2 activity and downstream pathways has major implications for human health. Recent Advances: Nrf2 regulates the transcription of components of the glutathione and thioredoxin antioxidant systems, as well as enzymes involved in phase I and phase II detoxification of exogenous and endogenous products, NADPH regeneration, and heme metabolism...
September 13, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28893839/mitochondrial-fission-facilitates-the-selective-mitophagy-of-protein-aggregates
#20
Jonathon L Burman, Sarah Pickles, Chunxin Wang, Shiori Sekine, Jose Norberto S Vargas, Zhe Zhang, Alice M Youle, Catherine L Nezich, Xufeng Wu, John A Hammer, Richard J Youle
Within the mitochondrial matrix, protein aggregation activates the mitochondrial unfolded protein response and PINK1-Parkin-mediated mitophagy to mitigate proteotoxicity. We explore how autophagy eliminates protein aggregates from within mitochondria and the role of mitochondrial fission in mitophagy. We show that PINK1 recruits Parkin onto mitochondrial subdomains after actinonin-induced mitochondrial proteotoxicity and that PINK1 recruits Parkin proximal to focal misfolded aggregates of the mitochondrial-localized mutant ornithine transcarbamylase (ΔOTC)...
September 11, 2017: Journal of Cell Biology
keyword
keyword
30089
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"