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In vivo protein protein interaction

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https://www.readbyqxmd.com/read/27914008/igf1r-dental-pulp-stem-cells-enhanced-neuroplasticity-in-hypoxia-ischemia-model
#1
Hsiao-Yu Chiu, Chen-Huan Lin, Chung Y Hsu, John Yu, Chia-Hung Hsieh, Woei-Cherng Shyu
Until now, the surface markers of multipotent mesenchymal stem cells (MSCs) had not been fully identified. Here, we found that the IGF1 receptor (IGF1R), regarded as a pluripotent marker of embryonic stem cells (ESCs), was also expressed in human dental pulp derived-mesenchymal stem cells (hDSCs), which displayed a potential for both self-renewal and multipotency. hDSC-secreted IGF1 interacted with IGF1R through an autocrine signaling pathway to maintain this self-renewal and proliferation potential. Stereotaxic implantation of immunosorted IGF1R(+) hDSCs in rats with neonatal hypoxia-ischemia (NHI) promoted neuroplasticity, improving the neurological outcome by increasing expression of the anti-apoptotic protein Bcl-2, which enhanced both neurogenesis and angiogenesis...
December 2, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27913309/sequence-determinants-of-the-caenhorhabditis-elegansdopamine-transporter-dictating-in-vivoaxonal-export-and-synaptic-localization
#2
Sarah B Robinson, J Andrew Hardaway, Shannon L Hardie, Jane Wright, Ryan M Glynn, Daniel P Bermingham, Qiao Han, Sarah M Sturgeon, Phyllis Freeman, Randy D Blakely
The monoamine neurotransmitter dopamine (DA) acts across phylogeny to modulate both simple and complex behaviors. The presynaptic DA transporter (DAT) is a major determinant of DA signaling capacity in ensuring efficient extracellular DA clearance. In humans, DAT is also a major target for prescribed and abused psychostimulants. Multiple structural determinants of DAT function and regulation have been defined, though largely these findings have arisen from heterologous expression or ex vivo cell culture studies...
November 29, 2016: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/27912076/activating-transcription-factor-3-is-essential-for-cigarette-smoke-induced-mucin-expression-via-interaction-with-activator-protein-1
#3
Yan-Ping Wu, Yin-Fang Wu, Chao Zhang, Hong-Bin Zhou, Chao Cao, Miao Li, Chen Zhu, Song-Min Ying, Zhi-Hua Chen, Hua-Hao Shen, Wen Li
Mucus hypersecretion is an important pathologic feature of chronic obstructive pulmonary disease. Activating transcription factor 3 (ATF3) is an adaptive-response gene that participates in various cellular processes. However, little is known about its role in cigarette smoke (CS)-induced mucus hyperproduction. This study aimed to investigate the role and molecular mechanisms of ATF3 in CS-induced Mucin 5AC (MUC5AC) expression. ATF3 was elevated in lung tissues of mice exposed to CS for 12 weeks. Treatment with CS extract significantly induced ATF3 expression and MUC5AC production in human bronchial epithelial cells, NCI-H292, and mouse tracheal epithelial cells...
November 29, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27911829/supramolecular-pegylation-of-biopharmaceuticals
#4
Matthew J Webber, Eric A Appel, Brittany Vinciguerra, Abel B Cortinas, Lavanya S Thapa, Siddharth Jhunjhunwala, Lyle Isaacs, Robert Langer, Daniel G Anderson
The covalent modification of therapeutic biomolecules has been broadly explored, leading to a number of clinically approved modified protein drugs. These modifications are typically intended to address challenges arising in biopharmaceutical practice by promoting improved stability and shelf life of therapeutic proteins in formulation, or modifying pharmacokinetics in the body. Toward these objectives, covalent modification with poly(ethylene glycol) (PEG) has been a common direction. Here, a platform approach to biopharmaceutical modification is described that relies on noncovalent, supramolecular host-guest interactions to endow proteins with prosthetic functionality...
November 28, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911712/regulation-of-receptor-type-protein-tyrosine-phosphatases-by-their-c-terminal-tail-domains
#5
REVIEW
Maayan Barnea, Tsviya Olender, Mark T Bedford, Ari Elson
Protein tyrosine phosphatases (PTPs) perform specific functions in vivo, despite being vastly outnumbered by their substrates. Because of this and due to the central roles PTPs play in regulating cellular function, PTP activity is regulated by a large variety of molecular mechanisms. We review evidence that indicates that the divergent C-terminal tail sequences (C-terminal domains, CTDs) of receptor-type PTPs (RPTPs) help regulate RPTP function by controlling intermolecular associations in a way that is itself subject to physiological regulation...
October 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27911494/determining-functional-aptamer-protein-interaction-by-biolayer-interferometry
#6
Xinhui Lou, Martin Egli, Xianbin Yang
Short single-stranded nucleic acids called aptamers are widely being explored as recognition molecules of high affinity and specificity for binding a wide range of target molecules, particularly protein targets. In biolayer interferometry (BLI), a simple Dip-and-Read approach in which the aptamer-coated biosensors are dipped into microplate wells is used to study the interactions between an aptamer and its target protein. Here we describe the protocol for the analysis of the interaction between a well-characterized anti-thrombin RNA aptamer with thrombin (Basic Protocol)...
December 1, 2016: Current Protocols in Nucleic Acid Chemistry
https://www.readbyqxmd.com/read/27910888/microtubule-stabilising-peptides-rescue-tau-phenotypes-in-vivo
#7
Shmma Quraishe, Megan Sealey, Louise Cranfield, Amritpal Mudher
The microtubule cytoskeleton is a highly dynamic, filamentous network underpinning cellular structure and function. In Alzheimer's disease, the microtubule cytoskeleton is compromised, leading to neuronal dysfunction and eventually cell death. There are currently no disease-modifying therapies to slow down or halt disease progression. However, microtubule stabilisation is a promising therapeutic strategy that is being explored. We previously investigated the disease-modifying potential of a microtubule-stabilising peptide NAP (NAPVSIPQ) in a well-established Drosophila model of tauopathy characterised by microtubule breakdown and axonal transport deficits...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909065/cdk5-directly-targets-nuclear-p21cip1-and-promotes-cancer-cell-growth
#8
Pao-Hsuan Huang, Mei-Chih Chen, Yu-Ting Peng, Wei-Hsiang Kao, Chih-Hsiang Chang, Yun-Chi Wang, Chih-Ho Lai, Jer-Tsong Hsieh, Jo-Hsin Wang, Yueh-Tsung Lee, Eugene Lin, Chia-Herng Yue, Hsin-Yi Wang, Shuen-Chi You, Ho Lin
The significance of Cdk5 in cell-cycle control and cancer biology has gained increased attention. Here we report the inverse correlation between the protein levels of Cdk5 and p21(CIP1) from cell-based and clinical analysis. Mechanistically, we identify that Cdk5 overexpression triggers the proteasome-dependent degradation of p21(CIP1) through a S130 phosphorylation in a Cdk2-independent manner. Besides, the evidence from cell-based and clinical analysis shows that Cdk5 primarily regulates nuclear p21(CIP1) protein degradation...
December 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27908976/a-novel-method-for-culturing-stellate-astrocytes-reveals-spatially-distinct-ca2-signaling-and-vesicle-recycling-in-astrocytic-processes
#9
Anne C Wolfes, Saheeb Ahmed, Ankit Awasthi, Markus A Stahlberg, Ashish Rajput, Daniel S Magruder, Stefan Bonn, Camin Dean
Interactions between astrocytes and neurons rely on the release and uptake of glial and neuronal molecules. But whether astrocytic vesicles exist and exocytose in a regulated or constitutive fashion is under debate. The majority of studies have relied on indirect methods or on astrocyte cultures that do not resemble stellate astrocytes found in vivo. Here, to investigate vesicle-associated proteins and exocytosis in stellate astrocytes specifically, we developed a simple, fast, and economical method for growing stellate astrocyte monocultures...
December 1, 2016: Journal of General Physiology
https://www.readbyqxmd.com/read/27908831/eukaryotic-translational-initiation-factor-4aii-reduces-the-replication-of-infectious-bursal-disease-virus-by-inhibiting-vp1-polymerase-activity
#10
Li Gao, Kai Li, Li Zhong, Lizhou Zhang, Xiaole Qi, Yongqiang Wang, Yulong Gao, Xiaomei Wang
Infectious bursal disease (IBD) is an acute, highly contagious, and immunosuppressive avian disease caused by IBD virus (IBDV). Although an interaction between eukaryotic translational initiation factor 4AII (eIF4AII) of the host and viral protein 1 (VP1), the RNA-dependent RNA polymerase (RdRp) of IBDV, has been established, the underlying effects of this interaction on IBDV and the molecular mechanism remain unclear. We here report that interaction of the host eIF4AII with VP1 inhibits the RNA polymerase activity of IBDV to reduce its replication in host cells...
November 28, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27908754/cyclic-citrullinated-mbp87-99-peptide-stimulates-t-cell-responses-implications-in-triggering-disease
#11
Vasso Apostolopoulos, George Deraos, Minos-Timotheos Matsoukas, Stephanie Day, Lily Stojanovska, Theodore Tselios, Maria-Eleni Androutsou, John Matsoukas
Amino acid mutations to agonist peptide epitopes of myelin proteins have been used to modulate immune responses and experimental autoimmune encephalomyelitis (EAE, animal model of multiple sclerosis). Such amino acid alteration are termed, altered peptide ligands (APL). We have shown that the agonist myelin basic protein (MBP) 87-99 epitope (MBP87-99) with crucial T cell receptor (TCR) substitutions at positions 91 and 96 (K(91),P(96) (TCR contact residues) to R(91),A(96); [R(91),A(96)]MBP87-99) results in altered T cell responses and inhibits EAE symptoms...
November 19, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27908613/sparc-interacts-with-actin-in-skeletal-muscle-in%C3%A2-vitro-and-in%C3%A2-vivo
#12
Louise H Jørgensen, Pia Lørup Jepsen, Anders Boysen, Line B Dalgaard, Lars G Hvid, Niels Ørtenblad, Dea Ravn, Jeeva Sellathurai, Jakob Møller-Jensen, Hanns Lochmüller, Henrik D Schrøder
The cytoskeleton is an integral part of skeletal muscle structure, and reorganization of the cytoskeleton occurs during various modes of remodeling. We previously found that the extracellular matrix protein secreted protein acidic and rich in cysteine (SPARC) is up-regulated and expressed intracellularly in developing muscle, during regeneration and in myopathies, which together suggests that SPARC might serve a specific role within muscle cells. Using co-immunoprecipitation combined with mass spectrometry and verified by staining for direct protein-protein interaction, we find that SPARC binds to actin...
November 28, 2016: American Journal of Pathology
https://www.readbyqxmd.com/read/27907247/ship2-structure-function-and-inhibition
#13
Mark P Thomas, Christophe Erneux, Barry V L Potter
SHIP2 is a phosphatase that acts at the 5-position of phosphatidylinositol 3,4,5-trisphosphate. It is one of several enzymes that catalyse dephosphorylation at the 5-position of phosphoinositides or inositol phosphates. SHIP2 has a confirmed role in opsismodysplasia, a disease of bone development, but also interacts with proteins involved in insulin signalling, cytoskeletal function (thus having an impact on endocytosis, adhesion, proliferation and apoptosis) and immune system function. The structure of three domains (constituting about 38% of the protein) is known...
November 30, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27907215/cd8-t-cells-induce-fatal-brainstem-pathology-during-cerebral-malaria-via-luminal-antigen-specific-engagement-of-brain-vasculature
#14
Phillip A Swanson, Geoffrey T Hart, Matthew V Russo, Debasis Nayak, Takele Yazew, Mirna Peña, Shahid M Khan, Chris J Janse, Susan K Pierce, Dorian B McGavern
Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection that results in thousands of deaths each year, mostly in African children. The in vivo mechanisms underlying this fatal condition are not entirely understood. Using the animal model of experimental cerebral malaria (ECM), we sought mechanistic insights into the pathogenesis of CM. Fatal disease was associated with alterations in tight junction proteins, vascular breakdown in the meninges / parenchyma, edema, and ultimately neuronal cell death in the brainstem, which is consistent with cerebral herniation as a cause of death...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27907175/p53-specifically-binds-triplex-dna-in-vitro-and-in-cells
#15
Marie Brázdová, Vlastimil Tichý, Robert Helma, Pavla Bažantová, Alena Polášková, Aneta Krejčí, Marek Petr, Lucie Navrátilová, Olga Tichá, Karel Nejedlý, Martin L Bennink, Vinod Subramaniam, Zuzana Bábková, Tomáš Martínek, Matej Lexa, Matej Adámik
Triplex DNA is implicated in a wide range of biological activities, including regulation of gene expression and genomic instability leading to cancer. The tumor suppressor p53 is a central regulator of cell fate in response to different type of insults. Sequence and structure specific modes of DNA recognition are core attributes of the p53 protein. The focus of this work is the structure-specific binding of p53 to DNA containing triplex-forming sequences in vitro and in cells and the effect on p53-driven transcription...
2016: PloS One
https://www.readbyqxmd.com/read/27907154/pheromone-recognition-and-selectivity-by-comr-proteins-among-streptococcus-species
#16
Erin Shanker, Donald A Morrison, Antoine Talagas, Sylvie Nessler, Michael J Federle, Gerd Prehna
Natural transformation, or competence, is an ability inherent to bacteria for the uptake of extracellular DNA. This process is central to bacterial evolution and allows for the rapid acquirement of new traits, such as antibiotic resistance in pathogenic microorganisms. For the Gram-positive bacteria genus Streptococcus, genes required for competence are under the regulation of quorum sensing (QS) mediated by peptide pheromones. One such system, ComRS, consists of a peptide (ComS) that is processed (XIP), secreted, and later imported into the cytoplasm, where it binds and activates the transcription factor ComR...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27906967/platinum-ii-iodido-complexes-of-7-azaindoles-with-significant-antiproliferative-effects-an-old-story-revisited-with-unexpected-outcomes
#17
Pavel Štarha, Ján Vančo, Zdeněk Trávníček, Jan Hošek, Jarmila Klusáková, Zdeněk Dvořák
A series of platinum(II) diiodido complexes containing 7-azaindole derivatives, having the general formula cis-[PtI2(naza)2] (1-8), has been prepared and thoroughly characterized, including X-ray structure analysis of cis-[PtI2(2Me4Claza)2]∙DMF (8∙DMF; 2Me4Claza = 2-methyl-4-chloro-7-azaindole). Complexes showed high in vitro cytotoxicity against nine human cancer cell lines (IC50 ranging from 0.4 to 12.8 μM), including the cisplatin-resistant ovarian cancer cell line (A2780R; IC50 = 1.0-3.5 μM). The results of in vivo testing, using the L1210 lymphocytic leukaemia model, at the equimolar doses of Pt with cisplatin (2 mg/kg) confirmed the activity of complex 8 comparable to cisplatin...
2016: PloS One
https://www.readbyqxmd.com/read/27906451/proximity-dependent-biotinylation-for-identification-of-interacting-proteins
#18
Valerie Le Sage, Alessandro Cinti, Andrew J Mouland
Complex interaction networks orchestrate key cellular processes including but not limited to transcription, translation, metabolism, and cell signaling. Delineating these interactions will aid in deciphering the regulation and function of these pathways and potential for manipulation. Proximity-dependent biotin identification (BioID) is quickly gaining popularity as a powerful tool for identifying novel protein-protein and proximity-based interactions in live cells. This technique relies on a promiscuous biotin ligase, which is fused to a protein of interest and, upon expression in the desired cell, will biotinylate proximal endogenous proteins...
December 1, 2016: Current Protocols in Cell Biology
https://www.readbyqxmd.com/read/27906185/anti-proliferative-activity-of-the-npm1-interacting-natural-product-avrainvillamide-in-acute-myeloid-leukemia
#19
Vibeke Andresen, Bjarte S Erikstein, Herschel Mukherjee, André Sulen, Mihaela Popa, Steinar Sørnes, Håkon Reikvam, Kok-Ping Chan, Randi Hovland, Emmet McCormack, Øystein Bruserud, Andrew G Myers, Bjørn T Gjertsen
Mutated nucleophosmin 1 (NPM1) acts as a proto-oncogene and is present in ~30% of patients with acute myeloid leukemia (AML). Here we examined the in vitro and in vivo anti-leukemic activity of the NPM1 and chromosome region maintenance 1 homolog (CRM1) interacting natural product avrainvillamide (AVA) and a fully syntetic AVA analog. The NPM1-mutated cell line OCI-AML3 and normal karyotype primary AML cells with NPM1 mutations were significantly more sensitive towards AVA than cells expressing wild-type (wt) NPM1...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27905407/endothelin-3-stimulates-cell-adhesion-and-cooperates-with-%C3%AE-1-integrins-during-enteric-nervous-system-ontogenesis
#20
Elodie Gazquez, Yuli Watanabe, Florence Broders-Bondon, Perrine Paul-Gilloteaux, Julie Heysch, Viviane Baral, Nadège Bondurand, Sylvie Dufour
Endothelin-3 (EDN3) and β1-integrins are required for the colonization of the embryonic gut by enteric neural crest cells (ENCCs) to form the enteric nervous system (ENS). β1-integrin-null ENCCs exhibit migratory defects in a region of the gut enriched in EDN3 and in specific extracellular matrix (ECM) proteins. We investigated the putative role of EDN3 on ENCC adhesion properties and its functional interaction with β1-integrins during ENS development. We show that EDN3 stimulates ENCC adhesion to various ECM components in vitro...
December 1, 2016: Scientific Reports
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