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14-3-3

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https://www.readbyqxmd.com/read/29142140/imaging-and-csf-analyses-effectively-distinguish-cjd-from-its-mimics
#1
Peter Rudge, Harpreet Hyare, Alison Green, John Collinge, Simon Mead
OBJECTIVE: To review clinical and investigation findings in patients referred to a specialist prion clinic who were suspected to have sporadic Creutzfeldt-Jakob disease (sCJD) and yet were found to have an alternative final diagnosis. METHODS: Review the clinical findings and investigations in 214 patients enrolled into the UK National Prion Monitoring Cohort Study between October 2008 and November 2015 who had postmortem confirmed sCJD and compare these features with 50 patients referred over the same period who had an alternative final diagnosis (CJD mimics)...
November 15, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29121962/direct-interaction-with-14-3-3%C3%AE-promotes-surface-expression-of-best1-channel-in-astrocyte
#2
Soo-Jin Oh, Junsung Woo, Young-Sun Lee, Minhee Cho, Eunju Kim, Nam-Chul Cho, Jae-Yong Park, Ae Nim Pae, C Justin Lee, Eun Mi Hwang
BACKGROUND: Bestrophin-1 (Best1) is a calcium-activated anion channel (CAAC) that is expressed broadly in mammalian tissues including the brain. We have previously reported that Best1 is expressed in hippocampal astrocytes at the distal peri-synaptic regions, called microdomains, right next to synaptic junctions, and that it disappears from the microdomains in Alzheimer's disease mouse model. Although Best1 appears to be dynamically regulated, the mechanism of its regulation and modulation is poorly understood...
November 9, 2017: Molecular Brain
https://www.readbyqxmd.com/read/29118970/14-3-3%C3%AE-loss-leads-to-neonatal-lethality-by-microrna-126-downregulation-mediated-developmental-defects-in-lung-vasculature
#3
Jun Yang, Sonali Joshi, Qingfei Wang, Ping Li, Hai Wang, Yan Xiong, Yi Xiao, Jinyang Wang, Jan Parker-Thornburg, Richard R Behringer, Dihua Yu
Background: The 14-3-3 family of proteins have been reported to play an important role in development in various mouse models, but the context specific developmental functions of 14-3-3ζ remain to be determined. In this study, we identified a context specific developmental function of 14-3-3ζ. Results: Targeted deletion of 14-3-3ζ in the C57Bl/6J murine genetic background led to neonatal lethality due to respiratory distress and could be rescued by out-breeding to the CD-1 or backcrossing to the FVB/NJ congenic background...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/29111562/expression-analysis-on-14-3-3-proteins-in-regenerative-liver-following-partial-hepatectomy
#4
Deming Xue, Yang Xue, Zhipeng Niu, Xueqiang Guo, Cunshuan Xu
14-3-3 proteins play a vital part in the regulation of cell cycle and apoptosis as signaling integration points. During liver regeneration, the quiescent hepatocytes go through hypertrophy and proliferation to restore liver weight. Therefore, we speculated that 14-3-3 proteins regulate the progression of liver regeneration. In this study, we analyzed the expression patterns of 14-3-3 proteins during liver regeneration of rat to provide an insight into the regenerative mechanism using western blotting. Only four isoforms (γ, ε, σ and τ/θ) of the 14-3-3 proteins were expressed in regenerative liver after partial hepatectomy (PH)...
November 6, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29110766/cerebrospinal-fluid-in-creutzfeldt-jakob-disease
#5
Inga Zerr, Saima Zafar, Matthias Schmitz, Franc Llorens
Cerebrospinal fluid (CSF) contains a dynamic and complex mixture of proteins, which reflects physiologic or pathologic states of the central nervous system. Changes in CSF proteome have been described in various neurodegenerative disorders. Earliest publications came from the field of prion disease. Two major approaches have been followed aiming to detect the pathologic form of prion protein (PrPSc) in various peripheral tissues on one hand, but also looking for surrogate parameters as a consequence of the underlying neurodegenerative process...
2017: Handbook of Clinical Neurology
https://www.readbyqxmd.com/read/29109150/role-of-salt-bridges-in-the-dimer-interface-of-14-3-3%C3%AE-in-dimer-dynamics-n-terminal-%C3%AE-helical-order-and-molecular-chaperone-activity
#6
Joanna M Woodcock, Katy L Goodwin, Jarrod J Sandow, Carl Coolen, Matthew A Perugini, Andrew I Webb, Stuart M Pitson, Angel F Lopez, John A Carver
The 14-3-3 family of intracellular proteins are dimeric, multi-functional adaptor proteins that bind to and regulate the activities of many important signaling proteins. The subunits within 14-3-3 dimers are predicted to be stabilized by salt bridges that are largely conserved across the 14-3-3 protein family and allow the different isoforms to form heterodimers. Here, we have examined the contributions of conserved salt-bridging residues in stabilizing the dimeric state of 14-3-3ζ. Using analytical ultracentrifugation, our results revealed that Asp-21 and Glu-89 both play key roles in dimer dynamics and contribute to dimer stability...
November 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29100370/identification-of-the-pak4-interactome-reveals-pak4-phosphorylation-of-n-wasp-and-promotion-of-arp2-3-dependent-actin-polymerization
#7
Miao Zhao, Matthias Spiess, Henrik J Johansson, Helene Olofsson, Jianjiang Hu, Janne Lehtiö, Staffan Strömblad
p21-activated kinase 4 (PAK4) regulates cell proliferation, apoptosis, cell motility and F-actin remodeling, but the PAK4 interactome has not been systematically analyzed. Here, we comprehensively characterized the human PAK4 interactome by iTRAQ quantitative mass spectrometry of PAK4-immunoprecipitations. Consistent with its multiple reported functions, the PAK4 interactome was enriched in diverse protein networks, including the 14-3-3, proteasome, replication fork, CCT and Arp2/3 complexes. Because PAK4 co-immunoprecipitated most subunits of the Arp2/3 complex, we hypothesized that PAK4 may play a role in Arp2/3 dependent actin regulation...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29095671/first-case-of-v180i-rare-mutation-in-a-brazilian-patient-with-creutzfeldt-jakob-disease
#8
Ricardo Krause Martinez de Souza, Nalini Drieli Josviak, Meire Silva Batistela, Paulo Sergio Faro Santos, Michele Christine Landemberger, Ricardo Ramina
Here, we report the first case of V180I rare mutation in a Brazilian woman whose clinical condition started with memory impairment for recent events and insomnia with 2 months of evolution, without any other alterations in neurological examination. Both the electroencephalogram (EEG) and the routine biochemical examination of cerebrospinal fluid (CSF) were normal. CSF 14-3-3 protein search was positive. Magnetic resonance imaging (MRI) of the encephalon showed findings suggestive of Creutzfeldt-Jakob disease, confirmed by sequencing of PRNP gene that reveal V180I mutation also homozygosity for methionine at codon 129 (M129M)...
November 2, 2017: Prion
https://www.readbyqxmd.com/read/29089450/mark3-mediated-phosphorylation-of-arhgef2-couples-microtubules-to-the-actin-cytoskeleton-to-establish-cell-polarity
#9
María-José Sandí, Christopher B Marshall, Marc Balan, Étienne Coyaud, Ming Zhou, Daniel M Monson, Noboru Ishiyama, Arun A Chandrakumar, José La Rose, Amber L Couzens, Anne-Claude Gingras, Brian Raught, Wei Xu, Mitsuhiko Ikura, Deborah K Morrison, Robert Rottapel
The PAR-1-MARK pathway controls cell polarity through the phosphorylation of microtubule-associated proteins. Rho-Rac guanine nucleotide exchange factor 2 (ARHGEF2), which activates Ras homolog family member A (RHOA), is anchored to the microtubule network and sequestered in an inhibited state through binding to dynein light chain Tctex-1 type 1 (DYNLT1). We showed in mammalian cells that liver kinase B1 (LKB1) activated the microtubule affinity-regulating kinase 3 (MARK3), which in turn phosphorylated ARHGEF2 at Ser(151) This modification disrupted the interaction between ARHGEF2 and DYNLT1 by generating a 14-3-3 binding site in ARHGEF2, thus causing ARHGEF2 to dissociate from microtubules...
October 31, 2017: Science Signaling
https://www.readbyqxmd.com/read/29075625/chemical-proteomics-for-target-discovery-of-head-to-tail-cyclized-mini-proteins
#10
Roland Hellinger, Kathrin Thell, Mina Vasileva, Taj Muhammad, Sunithi Gunasekera, Daniel Kümmel, Ulf Göransson, Christian W Becker, Christian W Gruber
Target deconvolution is one of the most challenging tasks in drug discovery, but a key step in drug development. In contrast to small molecules, there is a lack of validated and robust methodologies for target elucidation of peptides. In particular, it is difficult to apply these methods to cyclic and cysteine-stabilized peptides since they exhibit reduced amenability to chemical modification and affinity capture; however, such ribosomally synthesized and post-translationally modified peptide natural products are rich sources of promising drug candidates...
2017: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29075177/14-3-3-proteins-in-brain-development-neurogenesis-neuronal-migration-and-neuromorphogenesis
#11
REVIEW
Brett Cornell, Kazuhito Toyo-Oka
The 14-3-3 proteins are a family of highly conserved, multifunctional proteins that are highly expressed in the brain during development. Cumulatively, the seven 14-3-3 isoforms make up approximately 1% of total soluble brain protein. Over the last decade, evidence has accumulated implicating the importance of the 14-3-3 protein family in the development of the nervous system, in particular cortical development, and have more recently been recognized as key regulators in a number of neurodevelopmental processes...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29071385/protein-kinase-d-inhibitor-crt0066101-suppresses-bladder-cancer-growth-in-vitro-and-xenografts-via-blockade-of-the-cell-cycle-at-g2-m
#12
Qingdi Quentin Li, Iawen Hsu, Thomas Sanford, Reema Railkar, Navin Balaji, Carole Sourbier, Cathy Vocke, K C Balaji, Piyush K Agarwal
The protein kinase D (PKD) family of proteins are important regulators of tumor growth, development, and progression. CRT0066101, an inhibitor of PKD, has antitumor activity in multiple types of carcinomas. However, the effect and mechanism of CRT0066101 in bladder cancer are not understood. In the present study, we show that CRT0066101 suppressed the proliferation and migration of four bladder cancer cell lines in vitro. We also demonstrate that CRT0066101 blocked tumor growth in a mouse flank xenograft model of bladder cancer...
October 25, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29066278/structural-aspects-of-protein-kinase-ask1-regulation
#13
REVIEW
Tomas Obsil, Veronika Obsilova
Apoptosis signal-regulating kinase 1 (ASK1, also known as MAP3K5), a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family, activates the p38 mitogen-activated protein kinase and the c-Jun N-terminal kinase (JNK) signaling cascades in response to various stressors. ASK1 activity is tightly regulated through phosphorylation and interaction with various binding partners. However, the mechanistic details underlying the ASK1 regulation are still not fully understood. This review focuses on recent advances in structural studies of protein kinase ASK1 and on the insights they provide into its mechanism of regulation...
October 16, 2017: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29065217/the-fission-yeast-mapk-spc1-senses-perturbations-in-cdc25-and-wee1-activities-and-targets-rad24-to-restore-this-balance
#14
Madhurima Paul, Agamani Ghosal, Sushobhana Bandyopadhyay, G Prakadeeswari, Upasna Selvam, Neeraj Rai, Geetanjali Sundaram
Mitogen Activated Protein Kinases (MAPKs) play vital roles in multiple cellular processes and represent prominently pursued targets for development of therapeutic regimes. The MAPK Spc1 (p38 homolog) is known to be very important for both mitotic promotion and delay in Schizosaccharomyces pombe. However, the mechanism responsible for mitotic inhibition has remained elusive. Cdc25 (Cdc2 activator) and Wee1 (Cdc2 inhibtor) are important determinants of mitotic timing in all eukaryotes. Our results show that Spc1 can sense the perturbations in the balance of Cdc25 and Wee1 activities in S...
October 24, 2017: Yeast
https://www.readbyqxmd.com/read/29045841/phosphorylation-of-irhom2-controls-stimulated-proteolytic-shedding-by-the-metalloprotease-adam17-tace
#15
Miguel Cavadas, Ioanna Oikonomidi, Catarina J Gaspar, Emma Burbridge, Marina Badenes, Inês Félix, Alfonso Bolado, Tianyi Hu, Andrea Bileck, Christopher Gerner, Pedro M Domingos, Alex von Kriegsheim, Colin Adrain
Cell surface metalloproteases coordinate signaling during development, tissue homeostasis, and disease. TACE (TNF-α-converting enzyme), is responsible for cleavage ("shedding") of membrane-tethered signaling molecules, including the cytokine TNF, and activating ligands of the EGFR. The trafficking of TACE within the secretory pathway requires its binding to iRhom2, which mediates the exit of TACE from the endoplasmic reticulum. An important, but mechanistically unclear, feature of TACE biology is its ability to be stimulated rapidly on the cell surface by numerous inflammatory and growth-promoting agents...
October 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/29043964/accuracy-of-diagnosis-criteria-in-patients-with-suspected-diagnosis-of-sporadic-creutzfeldt-jakob-disease-and-detection-of-14-3-3-protein-france-1992-to-2009
#16
Laurene Peckeu, Nicole Delasnerie-Lauprètre, Jean-Philippe Brandel, Dominique Salomon, Véronique Sazdovitch, Jean-Louis Laplanche, Charles Duyckaerts, Danielle Seilhean, Stéphane Haïk, Jean-Jacques Hauw
Diagnostic criteria of Creutzfeldt-Jakob disease (CJD), a rare and fatal transmissible nervous system disease with public health implications, are determined by clinical data, electroencephalogram (EEG), detection of 14-3-3 protein in cerebrospinal fluid (CSF), brain magnetic resonance imaging and prion protein gene examination. The specificity of protein 14-3-3 has been questioned. We reviewed data from 1,572 autopsied patients collected over an 18-year period (1992-2009) and assessed whether and how 14-3-3 detection impacted the diagnosis of sporadic CJD in France, and whether this led to the misdiagnosis of treatable disorders...
October 2017: Euro Surveillance: Bulletin Européen sur les Maladies Transmissibles, European Communicable Disease Bulletin
https://www.readbyqxmd.com/read/29039919/the-molecular-tweezer-clr01-stabilizes-a-disordered-protein-protein-interface
#17
David Bier, Sumit Mittal, Kenny Bravo-Rodriguez, Andrea Sowislok, Xavier Guillory, Jeroen Briels, Christian Heid, Maria Bartel, Burkhard Wettig, Luc Brunsveld, Elsa Sanchez-Garcia, Thomas Schrader, Christian Ottmann
Protein regions that are involved in protein-protein interactions (PPIs) very often display a high degree of intrinsic disorder, which is reduced during the recognition process. A prime example is binding of the rigid 14-3-3 adapter proteins to their numerous partner proteins, whose recognition motifs undergo an extensive disorder-to-order transition. In this context, it is highly desirable to control this entropy-costly process using tailored stabilizing agents. This study reveals how the molecular tweezer CLR01 tunes the 14-3-3/Cdc25CpS216 protein-protein interaction...
November 2, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29036929/interaction-between-rho-gtpases-and-14-3-3-proteins
#18
REVIEW
Daniel Brandwein, Zhixiang Wang
The Rho GTPase family accounts for as many as 20 members. Among them, the archetypes RhoA, Rac1, and Cdc42 have been the most well-characterized. Like all members of the small GTPases superfamily, Rho proteins act as molecular switches to control cellular processes by cycling between active, GTP-bound and inactive, GDP-bound states. The 14-3-3 family proteins comprise seven isoforms. They exist as dimers (homo- or hetero-dimer) in cells. They function by binding to Ser/Thr phosphorylated intracellular proteins, which alters the conformation, activity, and subcellular localization of their binding partners...
October 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29032071/comparing-intestinal-versus-diffuse-gastric-cancer-using-a-peff-oriented-proteomic-pipeline
#19
Helisa Helena Wippel, Marlon Dias Mariano Santos, Milan Avila Clasen, Louise Ulrich Kurt, Fabio Cesar Sousa Nogueira, Carlos Eduardo Carvalho, Thaís Messias McCormick, Guilherme Pinto Bravo Neto, Lysangela Ronalte Alves, Maria da Gloria da Costa Carvalho, Paulo Costa Carvalho, Juliana de Saldanha da Gama Fischer
Gastric cancer is the fifth most common malignant neoplasia and the third leading cause of cancer death worldwide. Mac-Cormick et al. recently showed the importance of considering the anatomical region of the tumor in proteomic gastric cancer studies; more differences were found between distinct anatomical regions than when comparing healthy versus diseased tissue. Thus, failing to consider the anatomical region could lead to differential proteins that are not disease specific. With this as motivation, we compared the proteomic profiles of intestinal and diffuse adenocarcinoma from the same anatomical region, the corpus...
October 11, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28992755/drug-mediated-shortening-of-action-potentials-in-lqts2-human-induced-pluripotent-stem-cell-cardiomyocytes
#20
Gary Duncan, Karl Firth, Vinoj George, Minh Duc Hoang, Andrew Staniforth, Godfrey Smith, Chris Denning
Cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) are now a well-established modality for modeling genetic disorders of the heart. This is especially so for long QT syndrome (LQTS), which is caused by perturbation of ion channel function, and can lead to fainting, malignant arrhythmias and sudden cardiac death. LQTS2 is caused by mutations in KCNH2, a gene whose protein product contributes to IKr (also known as HERG), which is the predominant repolarizing potassium current in CMs...
October 9, 2017: Stem Cells and Development
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