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https://www.readbyqxmd.com/read/29444958/cdc48-and-ubiquilins-confer-selective-anterograde-protein-sorting-and-entry-into-the-multivesicular-body-in-yeast
#1
Rachel Kama, Galina Gabriely, Vydehi Kanneganti, Jeffrey E Gerst
Cdc48/p97 is known primarily for the retro-translocation of misfolded proteins in ER-associated protein degradation (ERAD). Here, we uncover a novel function for both Cdc48 and the conserved UBA-UBL ubiquitin receptor (ubiquilin) proteins in yeast ( e.g. Ddi1, Dsk2, Rad23), which deliver ubiquitinated proteins to the proteasome for degradation. We show that Cdc48, its core adaptors Npl4 and Ufd1, and the ubiquilins confer the constitutive anterograde delivery of carboxypeptidase S (Cps1), a membranal hydrolase, to the multivesicular body (MVB) and vacuolar lumen...
February 14, 2018: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/29414500/priapism-as-the-initial-sign-in-hematologic-disease-case-report-and-literature-review
#2
Luis Cuitláhuac Becerra-Pedraza, Luis Enrique Jiménez-Martínez, Iran Peña-Morfin, Rogelio Nava-Esquivel, Juan Alfredo Villegas-Martínez
INTRODUCTION: Priapism is an uncommon sign and sometimes considered a diagnosis challenge into systemic disease; this is defined as ≥4 h continuous penile erection, without sexual stimulation. We state that this work has been reported in line with the SCARE criteria PRESENTATION OF CASE: A Mexican 52-year-old man was brought to the emergency room with priapism of six days of evolution. His medical history reported fatigue and waxy pallor had begun a month ago, the rest of interrogation was unremarked...
January 12, 2018: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29406244/vitexin-protects-isoproterenol-induced-post-myocardial-injury-by-modulating-hipposignaling-and-er-stress-responses
#3
Rathinavel Ashokkumar, Sankar Jamuna, M S Sakeena Sadullah, S Niranjali Devaraj
The molecular mechanisms involved in ER stress-induced post myocardial injury remain elusive. In this study, we have investigated the molecular mechanism of ER stress-mediated myocyte death in Isoproterenol (ISO) induced myocardial infarction and its inhibition by a potent anti oxidant and anti-apoptotic bioflavonoid, Vitexin. ISO mediated apoptosis was found to be associated with ER permeabilization and characterized by enhanced production of ROS, activation of caspase-3, modulation of Bcl2 family proteins and activation of bnip3...
February 5, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29403277/understanding-the-translocation-mechanism-of-plga-nanoparticles-across-round-window-membrane-into-the-inner-ear-a-guideline-for-inner-ear-drug-delivery-based-on-nanomedicine
#4
Liping Zhang, Yuan Xu, Wenjuan Cao, Shibao Xie, Lu Wen, Gang Chen
Background: The round window membrane (RWM) functions as the primary biological barrier for therapeutic agents in the inner ear via local application. Previous studies on inner ear nano-drug delivery systems mostly focused on their pharmacokinetics and distribution in the inner ear, but seldom on the interaction with the RWM. Clarifying the transport mechanism of nanoparticulate carriers across RWM will shed more light on the optimum design of nano-drug delivery systems intended for meeting demands for their clinical application...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29369790/homeostatic-interplay-between-foxo-protein-and-er-proteostasis-in-cancer-and-other-diseases
#5
REVIEW
Matías González-Quiroz, Hery Urra, Celia María Limia, Claudio Hetz
Cancer cells are exposed to several adverse conditions within the tumor microenvironment that challenge cells to adapt and survive. Several of these homeostatic perturbations insults alter the normal function of the endoplasmic reticulum (ER), resulting in the accumulation of misfolded proteins. ER stress triggers a conserved signaling pathway known as the unfolded protein response (UPR) to cope with the stress or trigger apoptosis of damaged cells. The UPR has been described as a major driver of the acquisition of malignant characteristics that ultimately lead to tumor progression...
January 21, 2018: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29362229/mycoplasma-pneumoniae-community-acquired-respiratory-distress-syndrome-toxin-uses-a-novel-keled-sequence-for-retrograde-transport-and-subsequent-cytotoxicity
#6
Kumaraguruparan Ramasamy, Sowmya Balasubramanian, Krishnan Manickam, Lavanya Pandranki, Alexander B Taylor, P John Hart, Joel B Baseman, T R Kannan
Mycoplasma pneumoniae is an atypical bacterium that causes respiratory illnesses in humans, including pharyngitis, tracheobronchitis, and community-acquired pneumonia (CAP). It has also been directly linked to reactive airway disease, asthma, and extrapulmonary pathologies. During its colonization, M. pneumoniae expresses a unique ADP-ribosylating and vacuolating cytotoxin designated community-acquired respiratory distress syndrome (CARDS) toxin. CARDS toxin persists and localizes in the airway in CAP patients, asthmatics, and trauma patients with ventilator-associated pneumonia...
January 23, 2018: MBio
https://www.readbyqxmd.com/read/29361547/3d-correlative-electron-microscopy-reveals-continuity-of-brucella-containing-vacuoles-with-the-endoplasmic-reticulum
#7
Jaroslaw Sedzicki, Therese Tschon, Shyan Huey Low, Kevin Willemart, Kenneth N Goldie, Jean-Jacques Letesson, Henning Stahlberg, Christoph Dehio
Entry of the facultative intracellular pathogen Brucella into host cells results in the formation of endosomal Brucella-containing vacuoles (eBCVs) that initially traffic along the endocytic pathway. eBCV acidification triggers the expression of a type IV secretion system that translocates bacterial effector proteins into host cells. This interferes with lysosomal fusion of eBCVs and supports their maturation to replicative Brucella-containing vacuoles (rBCVs). Bacteria replicate in rBCVs to large numbers, eventually occupying most of the cytoplasmic volume...
January 12, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29358668/eif2%C3%AE-phosphorylation-is-pathognomonic-for-immunogenic-cell-death
#8
Lucillia Bezu, Allan Sauvat, Juliette Humeau, Lígia C Gomes-da-Silva, Kristina Iribarren, Sabrina Forveille, Pauline Garcia, Liwei Zhao, Peng Liu, Laurence Zitvogel, Laura Senovilla, Oliver Kepp, Guido Kroemer
The phosphorylation of eIF2α is essential for the endoplasmic reticulum (ER) stress response, the formation of stress granules, as well as macroautophagy. Several successful anticancer chemotherapeutics have the property to induce immunogenic cell death (ICD), thereby causing anticancer immune responses. ICD is accompanied by the translocation of calreticulin (CALR) from the ER lumen to the plasma membrane, which facilitates the transfer of tumor-associated antigens to dendritic cells. Here we systematically investigated the capacity of anticancer chemotherapeutics to induce signs of ER stress...
January 22, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29348368/defining-the-physiological-role-of-srp-in-protein-targeting-efficiency-and-specificity
#9
Elizabeth A Costa, Kelly Subramanian, Jodi Nunnari, Jonathan S Weissman
The signal recognition particle (SRP) enables cotranslational delivery of proteins for translocation into the endoplasmic reticulum (ER), but its full in vivo role remains incompletely explored. We combined rapid auxin-induced SRP degradation with proximity-specific ribosome profiling to define SRP's in vivo function in yeast. Despite the classic view that SRP recognizes N-terminal signal sequences, we show that SRP was generally essential for targeting transmembrane domains regardless of their position relative to the N terminus...
January 18, 2018: Science
https://www.readbyqxmd.com/read/29343547/molecular-pathways-for-immune-recognition-of-preproinsulin-signal-peptide-in-type-1-diabetes
#10
Deborah Kronenberg-Versteeg, Martin Eichmann, Mark A Russell, Arnoud de Ru, Beate Hehn, Norkhairin Yusuf, Peter A van Veelen, Sarah J Richardson, Noel G Morgan, Marius K Lemberg, Mark Peakman
The signal peptide region of preproinsulin (PPI) contains epitopes targeted by human leucocyte antigen-A (HLA-A)-restricted (HLA-A0201, A2402) cytotoxic T-cells as part of the pathogenesis of β-cell destruction in type 1 diabetes. We extended PPI epitope discovery to disease-associated HLA-B*1801 and HLA-B*3906 (risk) and HLA-A*1101 and HLA-B*3801 (protective) alleles revealing that 4/6 alleles present epitopes derived from the signal peptide region. During co-translational translocation of PPI, its signal peptide is cleaved and retained within the endoplasmic reticulum (ER) membrane, implying it is processed for immune recognition outside of the canonical, proteasome-directed pathway...
January 17, 2018: Diabetes
https://www.readbyqxmd.com/read/29320557/high-ahr-expression-in-breast-tumors-correlates-with-expression-of-genes-from-several-signaling-pathways-namely-inflammation-and-endogenous-tryptophan-metabolism
#11
Sophie Vacher, Patrice Castagnet, Walid Chemlali, François Lallemand, Didier Meseure, Marc Pocard, Ivan Bieche, Martine Perrot-Applanat
Increasing epidemiological and animal experimental data provide substantial support for the role of aryl hydrocarbon receptor (AhR) in mammary tumorigenesis. The effects of AhR have been clearly demonstrated in rodent models of breast carcinogenesis and in several established human breast cancer cell lines following exposure to AhR ligands or AhR overexpression. However, relatively little is known about the role of AhR in human breast cancers. AhR has always been considered to be a regulator of toxic and carcinogenic responses to environmental contaminants such as TCDD (dioxin) and benzo[a]pyrene (BaP)...
2018: PloS One
https://www.readbyqxmd.com/read/29317503/er-stress-mobilization-of-death-associated-protein-kinase-1-dependent-xenophagy-counteracts-mitochondria-stress-induced-epithelial-barrier-dysfunction
#12
Fernando Lopes, Åsa V Keita, Alpana Saxena, Jose Luis Reyes, Nicole Mancini, Ala Al Rajabi, Arthur Wang, Cristiane Baggio, Michael Dicay, Rob van Dalen, Younghee Ahn, Matheus Carneiro, Nathan Peters, Jong M Rho, Wallace MacNaughton, Stephan E Girardin, Humberto Jijon, Dana J Philpott, Johan D Söderholm, Derek M McKay
The gut microbiome contributes to inflammatory bowel disease (IBD), in which bacteria can be present within the epithelium. Epithelial barrier function is decreased in IBD, and dysfunctional epithelial mitochondria and endoplasmic reticulum (ER) stress have been individually associated with IBD. We therefore hypothesized that the combination of ER and mitochondrial stresses significantly disrupt epithelial barrier function. Here, we treated human colonic biopsies, epithelial colonoids, and epithelial cells with an uncoupler of oxidative phosphorylation, dinitrophenol (DNP), with or without the ER stressor tunicamycin, and assessed epithelial barrier function by monitoring internalization and translocation of commensal bacteria...
January 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29316847/chloroquine-promotes-the-recovery-of-acute-spinal-cord-injury-by-inhibiting-autophagy-associated-inflammation-and-endoplasmic-reticulum-stress
#13
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/29286473/a-simple-fluorescence-based-reporter-assay-to-identify-cellular-components-required-for-ricin-toxin-a-chain-rta-trafficking-in-yeast
#14
Björn Becker, Manfred J Schmitt
Bacterial and plant A/B toxins exploit the natural trafficking pathways in eukaryotic cells to reach their intracellular target(s) in the cytosol and to ultimately kill. Such A/B toxins generally consist of an enzymatically active Asubunit (e.g., ricin toxin A (RTA)) and one or more cell binding Bsubunit(s), which are responsible for toxin binding to specific cell surface receptors. Our current knowledge of how A/B toxins are capable of efficiently intoxicating cells helped scientists to understand fundamental cellular mechanisms, like endocytosis and intracellular protein sorting in higher eukaryotic cells...
December 15, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29281118/estrogen-deficiency-mediated-m2-macrophage-osteoclastogenesis-contributes-to-m1-m2-ratio-alteration-in-ovariectomized-osteoporotic-mice
#15
Ce Dou, Ning Ding, Chunrong Zhao, Tianyong Hou, Fei Kang, Zhen Cao, Chuan Liu, Yun Bai, Qijie Dai, Qinyu Ma, Fei Luo, Jianzhong Xu, Shiwu Dong
In this study, for the first time we discovered that M1/M2 ratio is increased in bone marrow of ovariectomized (OVX) osteoporotic C57BL/6 mice. Considering estrogen is the main variable, we assumed that estrogen participated in this alteration. To determine whether and how estrogen contributes to the change of M1/M2 ratio, we first isolated bone marrow macrophages (BMMs) from mice femur and stimulated the cells with lipopolysaccharide (LPS)/Interferon (IFN)-γ for M1 polarization and interleukin (IL)-4/IL-13 for M2 polarization...
December 27, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29246967/targeting-and-translocation-of-proteins-to-the-endoplasmic-reticulum-at-a-glance
#16
REVIEW
Naama Aviram, Maya Schuldiner
The evolutionary emergence of organelles was a defining process in diversifying biochemical reactions within the cell and enabling multicellularity. However, compartmentalization also imposed a great challenge-the need to import proteins synthesized in the cytosol into their respective sites of function. For example, one-third of all genes encode for proteins that must be targeted and translocated into the endoplasmic reticulum (ER), which serves as the entry site to the majority of endomembrane compartments...
December 15, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/29243589/defective-stim-mediated-store-operated-ca2-entry-in-hepatocytes-leads-to-metabolic-dysfunction-in-obesity
#17
Ana Paula Arruda, Benedicte Mengel Pers, Günes Parlakgul, Ekin Güney, Ted Goh, Erika Cagampan, Grace Yankun Lee, Renata L Goncalves, Gökhan S Hotamisligil
Defective Ca2+ handling is a key mechanism underlying hepatic endoplasmic reticulum (ER) dysfunction in obesity. ER Ca2+ level is in part monitored by the store-operated Ca2+ entry (SOCE) system, an adaptive mechanism that senses ER luminal Ca2+ concentrations through the STIM proteins and facilitates import of the ion from the extracellular space. Here, we show that hepatocytes from obese mice displayed significantly diminished SOCE as a result of impaired STIM1 translocation, which was associated with aberrant STIM1 O-GlycNAcylation...
December 15, 2017: ELife
https://www.readbyqxmd.com/read/29241549/trafficking-mediated-sting-degradation-requires-sorting-to-acidified-endolysosomes-and-can-be-targeted-to-enhance-anti-tumor-response
#18
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/29229776/positive-charge-in-the-n-region-of-the-signal-peptide-contributes-to-efficient-post-translational-translocation-of-small-secretory-preproteins
#19
Huan Guo, Jinhong Sun, Xin Li, Yi Xiong, Heting Wang, Hua Shu, Ruimin Zhu, Qi Liu, Yumeng Huang, Rachel Madley, Yulun Wang, Jingqiu Cui, Peter Arvan, Ming Liu
Increasing evidence indicates that many small secretory preproteins can undergo post-translational translocation across the membrane of the endoplasmic reticulum (ER). Although the cellular machinery involved in post-translational translocation of small secretory preproteins has begun to be elucidated, the intrinsic signals contained within these small secretory preproteins that contribute to their efficient post-translational translocation remain unknown. Here, we analyzed the eukaryotic secretory proteome and discovered that it contains an increased percentage of small secretory preproteins with a positive charge in the n-region of the signal peptide (SP)...
December 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29229738/hdac5-integrates-er-stress-and-fasting-signals-to-regulate-hepatic-fatty-acid-oxidation
#20
Xinchen Qiu, Jian Li, Sihan Lv, Jiamin Yu, Junkun Jiang, Jindong Yao, Yang Xiao, Bingxin Xu, Haiyan He, Fangfei Guo, Zhen-Ning Zhang, Chao Zhang, Bing Luan
Disregulation of fatty acid oxidation, one of the major mechanisms to maintain hepatic lipid homeostasis under fasting conditions, leads to hepatic steatosis. Although obesity and type 2 diabetes-induced ER stress contributes to hepatic steatosis, it is largely unknown how ER stress regulates fatty acid oxidation. Here we show that fasting glucagon stimulates the dephosphorylation and nuclear translocation of HDAC5, where it interacts with PPARα and promotes transcriptional activity of PPARα. As a result, overexpression of HDAC5 but not PPARα binding-deficient HDAC5 in liver improves lipid homeostasis, while RNAi-mediated knockdown of HDAC5 deteriorates hepatic steatosis...
December 11, 2017: Journal of Lipid Research
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