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https://www.readbyqxmd.com/read/28643412/rhodium-i-catalyzed-bridged-5-2-cycloaddition-of-cis-allene-vinylcyclopropanes-to-synthesize-the-bicyclo-4-3-1-decane-skeleton
#1
Cheng-Hang Liu, Zhi-Xiang Yu
Previously reported was that cis-ene-vinylcyclopropanes (cis-ene-VCPs) underwent Rh-catalyzed [5+2] reaction to give 5,7-fused bicyclic products, where vinylcyclopropane (VCP) acts as five-carbon synthon. Unfortunately, this reaction had very limited scope. Replacing the 2π component of cis-ene-VCPs to allene moiety, the corresponding cis-allene-VCPs did not undergo the expected normal [5+2] cycloaddition to give 5,7-fused bicyclic products. Instead, the challenging bicyclo[4.3.1]decane skeleton was obtained via an unprecedented bridged [5+2] cycloaddition...
June 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28611990/structure-and-function-of-p97-and-pex1-6-type-ii-aaa-complexes
#2
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
https://www.readbyqxmd.com/read/28590308/perioperative-factors-related-to-the-severity-of-vocal-cord-paralysis-after-thoracic-cardiovascular-surgery-a-retrospective-review
#3
Hiroki Taenaka, Sho Carl Shibata, Kenta Okitsu, Takeshi Iritakenishi, Tatsuyuki Imada, Akinori Uchiyama, Yuji Fujino
BACKGROUND: Vocal cord paralysis (VCP) is a rare complication of thoracic cardiovascular surgery. In severe cases, life-threatening airway obstruction may occur. OBJECTIVE: To evaluate the incidence and severity of VCP among patients who underwent thoracic cardiovascular surgery and to identify possible risk factors. DESIGN: Single-centre retrospective review of adult patients. SETTING: Osaka University Hospital, Suita, Japan, from January 2013 to August 2015...
July 2017: European Journal of Anaesthesiology
https://www.readbyqxmd.com/read/28575658/rfwd3-mediated-ubiquitination-promotes-timely-removal-of-both-rpa-and-rad51-from-dna-damage-sites-to-facilitate-homologous-recombination
#4
Shojiro Inano, Koichi Sato, Yoko Katsuki, Wataru Kobayashi, Hiroki Tanaka, Kazuhiro Nakajima, Shinichiro Nakada, Hiroyuki Miyoshi, Kerstin Knies, Akifumi Takaori-Kondo, Detlev Schindler, Masamichi Ishiai, Hitoshi Kurumizaka, Minoru Takata
RFWD3 is a recently identified Fanconi anemia protein FANCW whose E3 ligase activity toward RPA is essential in homologous recombination (HR) repair. However, how RPA ubiquitination promotes HR remained unknown. Here, we identified RAD51, the central HR protein, as another target of RFWD3. We show that RFWD3 polyubiquitinates both RPA and RAD51 in vitro and in vivo. Phosphorylation by ATR and ATM kinases is required for this activity in vivo. RFWD3 inhibits persistent mitomycin C (MMC)-induced RAD51 and RPA foci by promoting VCP/p97-mediated protein dynamics and subsequent degradation...
June 1, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28575052/myogenic-differentiation-of-vcp-disease-induced-pluripotent-stem-cells-a-novel-platform-for-drug-discovery
#5
Katrina J Llewellyn, Angèle Nalbandian, Lan N Weiss, Isabela Chang, Howard Yu, Bibo Khatib, Baichang Tan, Vanessa Scarfone, Virginia E Kimonis
Valosin Containing Protein (VCP) disease is an autosomal dominant multisystem proteinopathy caused by mutations in the VCP gene, and is primarily associated with progressive muscle weakness, including atrophy of the pelvic and shoulder girdle muscles. Currently, no treatments are available and cardiac and respiratory failures can lead to mortality at an early age. VCP is an AAA ATPase multifunction complex protein and mutations in the VCP gene resulting in disrupted autophagic clearance. Due to the rarity of the disease, the myopathic nature of the disorder, ethical and practical considerations, VCP disease muscle biopsies are difficult to obtain...
2017: PloS One
https://www.readbyqxmd.com/read/28573364/-genetic-architecture-of-amyotrophic-lateral-sclerosis-and-frontotemporal-dementia-overlap-and-differences
#6
REVIEW
M Synofzik, M Otto, A Ludolph, J H Weishaupt
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) overlap not only clinically, but also with respect to shared neuropathology and genes. A large number of novel genes has recently been identified which underlie both diseases, e. g., C9orf72, TARDBP, GRN, TBK1, UBQLN2, VCP, CHCHD10, or SQSTM1. In contrast, other genes are still largely associated with only one of the two diseases, e. g., SOD1 with ALS or MAPT with FTD. These genetic findings indicate a large number of shared mechanisms, yet along with still a certain cell-specific vulnerability...
June 1, 2017: Der Nervenarzt
https://www.readbyqxmd.com/read/28564594/progressive-motor-neuron-pathology-and-the-role-of-astrocytes-in-a-human-stem-cell-model-of-vcp-related-als
#7
Claire E Hall, Zhi Yao, Minee Choi, Giulia E Tyzack, Andrea Serio, Raphaelle Luisier, Jasmine Harley, Elisavet Preza, Charlie Arber, Sarah J Crisp, P Marc D Watson, Dimitri M Kullmann, Andrey Y Abramov, Selina Wray, Russell Burley, Samantha H Y Loh, L Miguel Martins, Molly M Stevens, Nicholas M Luscombe, Christopher R Sibley, Andras Lakatos, Jernej Ule, Sonia Gandhi, Rickie Patani
Motor neurons (MNs) and astrocytes (ACs) are implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), but their interaction and the sequence of molecular events leading to MN death remain unresolved. Here, we optimized directed differentiation of induced pluripotent stem cells (iPSCs) into highly enriched (> 85%) functional populations of spinal cord MNs and ACs. We identify significantly increased cytoplasmic TDP-43 and ER stress as primary pathogenic events in patient-specific valosin-containing protein (VCP)-mutant MNs, with secondary mitochondrial dysfunction and oxidative stress...
May 30, 2017: Cell Reports
https://www.readbyqxmd.com/read/28551275/genetic-analysis-of-vcp-and-wash-complex-genes-in-a-german-cohort-of-sporadic-als-ftd-patients
#8
Matthias Türk, Rolf Schröder, Katharina Khuller, Andreas Hofmann, Carolin Berwanger, Albert C Ludolph, Gabriele Dekomien, Kathrin Müller, Jochen H Weishaupt, Christian T Thiel, Christoph S Clemen
Mutations of the human valosin-containing protein, p97 (VCP) and Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex genes cause motor neuron and cognitive impairment disorders. Here, we analyzed a cohort of German patients with sporadic amyotrophic lateral sclerosis and frontotemporal lobar degeneration comorbidity (ALS/FTD) for VCP and WASH complex gene mutations. Next-generation panel sequencing of VCP, WASH1, FAM21C, CCDC53, SWIP, strumpellin, F-actin capping protein of muscle Z-line alfa 1 (CAPZA1), and CAPZB genes was performed in 43 sporadic ALS/FTD patients...
May 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28540836/vocal-cord-paresis-following-single-session-high-intensity-focused-ablation-hifu-treatment-of-benign-thyroid-nodules-incidence-and-risk-factors
#9
Brian H H Lang, Yu-Cho Woo, Keith Wan-Hang Chiu
BACKGROUND: Vocal cord paresis (VCP) may occur following high intensity focused ultrasound (HIFU) of thyroid nodules. We hypothesised its occurrence relates to the distance of the focus point (FP) of the HIFU beams from the recurrent laryngeal nerve (RLN) and the thermal power that this point received. Their relationships were examined. METHODS: One hundred and three patients who underwent HIFU for symptomatic benign thyroid nodule from October 2015 to March 2017 were analysed...
June 6, 2017: International Journal of Hyperthermia
https://www.readbyqxmd.com/read/28526689/long-non-coding-rna-neat1-promotes-hepatocellular-carcinoma-cell-proliferation-through-the-regulation-of-mir-129-5p-vcp-i%C3%AE%C2%BAb
#10
Luo Fang, Jiao Sun, Zongfu Pan, Yu Song, Like Zhong, Yiwen Zhang, Yujia Liu, Xiaowei Zheng, Ping Huang
BACKGROUND: Long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) plays an important role in the pathogenesis and development of several types of cancer. However, the functional mechanism of NEAT1 in hepatocellular carcinoma (HCC) remains unclear. METHODS: The NEAT1 and miR-129-5p expression in HCC tissues and cell lines were quantified by means of qPCR. The effects of NEAT1 expression inhibition or up-regulation in HCC cell lines were analyzed in terms of cell viability and apoptosis...
May 19, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28524179/a-fkbp5-mutation-is-associated-with-paget-s-disease-of-bone-and-enhances-osteoclastogenesis
#11
Bingru Lu, Yulian Jiao, Yinchang Wang, Jing Dong, Muyun Wei, Bin Cui, Yafang Sun, Laicheng Wang, Bingchang Zhang, Zijiang Chen, Yueran Zhao
Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28512218/ubiquitin-and-atp-dependent-unfoldase-activity-of-p97-vcp%C3%A2-nploc4%C3%A2-ufd1l-is-enhanced-by-a-mutation-that-causes-multisystem-proteinopathy
#12
Emily E Blythe, Kristine C Olson, Vincent Chau, Raymond J Deshaies
p97 is a "segregase" that plays a key role in numerous ubiquitin (Ub)-dependent pathways such as ER-associated degradation. It has been hypothesized that p97 extracts proteins from membranes or macromolecular complexes to enable their proteasomal degradation; however, the complex nature of p97 substrates has made it difficult to directly observe the fundamental basis for this activity. To address this issue, we developed a soluble p97 substrate-Ub-GFP modified with K48-linked ubiquitin chains-for in vitro p97 activity assays...
May 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28498200/evaluating-the-veterans-choice-program-lessons-for-developing-a-high-performing-integrated-network
#13
Kristin M Mattocks, Baligh Yehia
No abstract text is available yet for this article.
July 2017: Medical Care
https://www.readbyqxmd.com/read/28494016/the-host-ubiquitin-dependent-segregase-vcp-p97-is-required-for-the-onset-of-human-cytomegalovirus-replication
#14
Yao-Tang Lin, James Prendergast, Finn Grey
The human cytomegalovirus major immediate early proteins IE1 and IE2 are critical drivers of virus replication and are considered pivotal in determining the balance between productive and latent infection. IE1 and IE2 are derived from the same primary transcript by alternative splicing and regulation of their expression likely involves a complex interplay between cellular and viral factors. Here we show that knockdown of the host ubiquitin-dependent segregase VCP/p97, results in loss of IE2 expression, subsequent suppression of early and late gene expression and, ultimately, failure in virus replication...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28475898/molecular-mechanism-of-substrate-processing-by-the-cdc48-atpase-complex
#15
Nicholas O Bodnar, Tom A Rapoport
The Cdc48 ATPase and its cofactors Ufd1/Npl4 (UN) extract polyubiquitinated proteins from membranes or macromolecular complexes, but how they perform these functions is unclear. Cdc48 consists of an N-terminal domain that binds UN and two stacked hexameric ATPase rings (D1 and D2) surrounding a central pore. Here, we use purified components to elucidate how the Cdc48 complex processes substrates. After interaction of the polyubiquitin chain with UN, ATP hydrolysis by the D2 ring moves the polypeptide completely through the double ring, generating a pulling force on the substrate and causing its unfolding...
May 4, 2017: Cell
https://www.readbyqxmd.com/read/28451587/the-interplay-of-cofactor-interactions-and-post-translational-modifications-in-the-regulation-of-the-aaa-atpase-p97
#16
REVIEW
Petra Hänzelmann, Hermann Schindelin
The hexameric type II AAA ATPase (ATPase associated with various activities) p97 (also referred to as VCP, Cdc48, and Ter94) is critically involved in a variety of cellular activities including pathways such as DNA replication and repair which both involve chromatin remodeling, and is a key player in various protein quality control pathways mediated by the ubiquitin proteasome system as well as autophagy. Correspondingly, p97 has been linked to various pathophysiological states including cancer, neurodegeneration, and premature aging...
2017: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/28443643/faf1-phosphorylation-by-akt-accumulates-tgf-%C3%AE-type-ii-receptor-and-drives-breast-cancer-metastasis
#17
Feng Xie, Ke Jin, Li Shao, Yao Fan, Yifei Tu, Yihao Li, Bin Yang, Hans van Dam, Peter Ten Dijke, Honglei Weng, Steven Dooley, Shuai Wang, Junling Jia, Jin Jin, Fangfang Zhou, Long Zhang
TGF-β is pro-metastatic for the late-stage breast cancer cells. Despite recent progress, the regulation of TGF-β type II receptor remains uncertain. Here we report that FAF1 destabilizes TβRII on the cell surface by recruiting the VCP/E3 ligase complex, thereby limiting excessive TGF-β response. Importantly, activated AKT directly phosphorylates FAF1 at Ser 582, which disrupts the FAF1-VCP complex and reduces FAF1 at the plasma membrane. The latter results in an increase in TβRII at the cell surface that promotes both TGF-β-induced SMAD and non-SMAD signalling...
April 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28430856/a-comprehensive-analysis-of-rare-genetic-variation-in-amyotrophic-lateral-sclerosis-in-the-uk
#18
Sarah Morgan, Aleksey Shatunov, William Sproviero, Ashley R Jones, Maryam Shoai, Deborah Hughes, Ahmad Al Khleifat, Andrea Malaspina, Karen E Morrison, Pamela J Shaw, Christopher E Shaw, Katie Sidle, Richard W Orrell, Pietro Fratta, John Hardy, Alan Pittman, Ammar Al-Chalabi
Amyotrophic lateral sclerosis is a progressive neurodegenerative disease of motor neurons. About 25 genes have been verified as relevant to the disease process, with rare and common variation implicated. We used next generation sequencing and repeat sizing to comprehensively assay genetic variation in a panel of known amyotrophic lateral sclerosis genes in 1126 patient samples and 613 controls. About 10% of patients were predicted to carry a pathological expansion of the C9orf72 gene. We found an increased burden of rare variants in patients within the untranslated regions of known disease-causing genes, driven by SOD1, TARDBP, FUS, VCP, OPTN and UBQLN2...
June 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28425440/the-valosin-containing-protein-is-a-novel-mediator-of-mitochondrial-respiration-and-cell-survival-in-the-heart-in-vivo
#19
Paulo Lizano, Eman Rashed, Shaunrick Stoll, Ning Zhou, Hairuo Wen, Tristan T Hays, Gangjian Qin, Lai-Hua Xie, Christophe Depre, Hongyu Qiu
The valosin-containing protein (VCP) participates in signaling pathways essential for cell homeostasis in multiple tissues, however, its function in the heart in vivo remains unknown. Here we offer the first description of the expression, function and mechanism of action of VCP in the mammalian heart in vivo in both normal and stress conditions. By using a transgenic (TG) mouse with cardiac-specific overexpression (3.5-fold) of VCP, we demonstrate that VCP is a new and powerful mediator of cardiac protection against cell death in vivo, as evidenced by a 50% reduction of infarct size after ischemia/reperfusion versus wild type...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28423563/regulation-of-p53wt-glioma-cell-proliferation-by-androgen-receptor-mediated-inhibition-of-small-vcp-p97-interacting-protein-expression
#20
Dejun Bao, Chuandong Cheng, Xiaoqiang Lan, Rong Xing, Zhuo Chen, Hua Zhao, Junyan Sun, Yang Wang, Chaoshi Niu, Bo Zhang, Shengyun Fang
The incidence of glioma in men is higher than that in women; however, little is known about the expression and basic function of the androgen receptor (AR) in gliomas. AR inhibited the small VCP/p97-interacting protein (SVIP) on the transcriptional level was previously reported. The present study shows that the protein level of AR is highly expressed in cell lines of the nervous system. Moreover, the AR expression is increased while SVIP expression is decreased in tumor tissue of glioma patients, which is in agreement with the progressing WHO grades...
April 4, 2017: Oncotarget
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