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In vivo protein protein interaction

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https://www.readbyqxmd.com/read/28346425/chip-stub1-regulates-the-warburg-effect-by-promoting-degradation-of-pkm2-in-ovarian-carcinoma
#1
Y Shang, J He, Y Wang, Q Feng, Y Zhang, J Guo, J Li, S Li, Y Wang, G Yan, F Ren, Y Shi, J Xu, N Zeps, Y Zhai, D He, Z Chang
Tumor cells preferentially adopt aerobic glycolysis for their energy supply, a phenomenon known as the Warburg effect. It remains a matter of debate as to how the Warburg effect is regulated during tumor progression. Here, we show that CHIP (carboxyl terminus of Hsc70-interacting protein), a U-box E3 ligase, suppresses tumor progression in ovarian carcinomas by inhibiting aerobic glycolysis. While CHIP is downregulated in ovarian carcinoma, induced expression of CHIP results in significant inhibition of the tumor growth examined by in vitro and in vivo experiments...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346422/the-metastatic-suppressor-ndrg1-inhibits-emt-migration-and-invasion-through-interaction-and-promotion-of-caveolin-1-ubiquitylation-in-human-colorectal-cancer-cells
#2
L Mi, F Zhu, X Yang, J Lu, Y Zheng, Q Zhao, X Wen, A Lu, M Wang, M Zheng, J Ji, J Sun
N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28346102/phage-display-derived-ligand-for-mucosal-transcytotic-receptor-gp-2-promotes-antigen-delivery-to-m-cells-and-induces-antigen-specific-immune-response
#3
Inam Ullah Khan, Jiansheng Huang, Rui Liu, Jingbo Wang, Jun Xie, Naishuo Zhu
Successful oral immunization depends on efficient delivery of antigens (Ags) to the mucosal immune induction site. Glycoprotein-2 (GP-2) is an integral membrane protein that is expressed specifically on M cells within follicle-associated epithelium (FAE) and serves as transcytotic receptor for luminal Ags. In this study, we selected peptide ligands against recombinant human GP-2 by screening a phage display library and evaluated their interaction with GP-2 in vitro and ex vivo. Selected peptides were conjugated to the C-terminal of enhanced green fluorescence protein (EGFP) and evaluated for their ability to induce an immune response in mice...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345876/engineering-cellular-microenvironments-with-photo-and-enzymatically-responsive-hydrogels-toward-biomimetic-3d-cell-culture-models
#4
Roger Y Tam, Laura J Smith, Molly S Shoichet
Conventional cell culture techniques using 2D polystyrene or glass have provided great insight into key biochemical mechanisms responsible for cellular events such as cell proliferation, differentiation, and cell-cell interactions. However, the physical and chemical properties of 2D culture in vitro are dramatically different than those found in the native cellular microenvironment in vivo. Cells grown on 2D substrates differ significantly from those grown in vivo, and this explains, in part, why many promising drug candidates discovered through in vitro drug screening assays fail when they are translated to in vivo animal or human models...
March 27, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28344321/broad-spectrum-antiviral-activity-for-paramyxoviruses-is-modulated-by-biophysical-properties-of-fusion-inhibitory-peptides
#5
Cyrille Mathieu, Marcelo T Augusto, Stefan Niewiesk, Branka Horvat, Laura M Palermo, Giuseppina Sanna, Silvia Madeddu, Devra Huey, Miguel A R B Castanho, Matteo Porotto, Nuno C Santos, Anne Moscona
Human paramyxoviruses include global causes of lower respiratory disease like the parainfluenza viruses, as well as agents of lethal encephalitis like Nipah virus. Infection is initiated by viral glycoprotein-mediated fusion between viral and host cell membranes. Paramyxovirus viral fusion proteins (F) insert into the target cell membrane, and form a transient intermediate that pulls the viral and cell membranes together as two heptad-repeat regions refold to form a six-helix bundle structure that can be specifically targeted by fusion-inhibitory peptides...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28344320/dpp4-truncated-gm-csf-il-3-manifest-distinct-receptor-binding-regulatory-functions-compared-to-their-full-length-forms
#6
H A O'Leary, M Capitano, S Cooper, C Mantel, H S Boswell, R Kapur, B Ramdas, R Chan, L Deng, C-K Qu, H E Broxmeyer
Dipeptidylpeptidase 4 (DPP4/CD26) enzymatically cleaves select penultimate amino acids of proteins, including colony stimulating factors (CSFs), and has been implicated in cellular regulation. To better understand the role of DPP4 regulation of hematopoiesis, we analyzed the activity of DPP4 on the surface of immature blood cells and then comparatively assessed the interactions and functional effects of full-length (FL) and DPP4 truncated factors [(T)-GM-CSF and- IL-3] on both in vitro and in vivo models of normal and leukemic cells...
March 27, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28344018/enhanced-topical-penetration-system-exposure-and-anti-psoriasis-activity-of-two-particle-sized-curcumin-loaded-plga-nanoparticles-in-hydrogel
#7
Lin Sun, Zeyu Liu, Lun Wang, Dongmei Cun, Henry H Y Tong, Ru Yan, Xin Chen, Ruibing Wang, Ying Zheng
Psoriasis is an immune-mediated skin disorder, which is triggered by the aberrant activation of dendritic cells in skin. This activation is followed by the complex interaction between the immune cells in the skin and keratinocyte in the epidermis. To improve the conditions of poor aqueous solubility and chemical stability, overcome skin barriers, and enhance in-vivo anti-psoriatic activity, curcumin (Cur) loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) were fabricated and administered by topical route to treat Imiquimod (IMQ)-induced psoriasis-like mouse model...
March 23, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28343944/rack1-cooperates-with-nras-q61k-to-promote-melanoma-in-vivo
#8
C Campagne, E Reyes-Gomez, M E Picco, S Loiodice, P Salaun, J Ezagal, F Bernex, P H Commère, S Pons, D Esquerre, E Bourneuf, J Estellé, U Maskos, P Lopez-Bergami, G Aubin-Houzelstein, J J Panthier, G Egidy
Melanoma is the deadliest skin cancer. RACK1 (Receptor for activated protein kinase C) protein was proposed as a biological marker of melanoma in human and domestic animal species harboring spontaneous melanomas. As a scaffold protein, RACK1 is able to coordinate the interaction of key signaling molecules implicated in both physiological cellular functions and tumorigenesis. A role for RACK1 in rewiring ERK and JNK signaling pathways in melanoma cell lines had been proposed. Here, we used a genetic approach to test this hypothesis in vivo in the mouse...
March 23, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28343913/sumoylation-inhibition-mediated-by-disruption-of-sumo-e1-e2-interactions-confers-plant-susceptibility-to-necrotrophic-fungal-pathogens
#9
Laura Castaño-Miquel, Abraham Mas, Inês Teixeira, Josep Seguí, Anna Perearnau, Bhagyasree N Thampi, Arnaldo L Schapire, Natalia Rodrigo, Gaelle La Verde, Silvia Manrique, Maria Coca, L Maria Lois
Protein modification by SUMO modulates essential biological processes in eukaryotes. SUMOylation is facilitated by sequential action of the E1-activating, E2-conjugating, and E3-ligase enzymes. In plants, SUMO regulates plant development and stress responses, which are key determinants in agricultural productivity. To generate additional tools for advancing our knowledge about the SUMO biology, we have developed a strategy for inhibiting in vivo SUMO conjugation based on disruption of SUMO E1-E2 interactions through expression of E1 SAE2(UFDCt) domain...
February 14, 2017: Molecular Plant
https://www.readbyqxmd.com/read/28343687/multiple-simultaneous-independent-gradients-for-a-versatile-multidimensional-liquid-chromatography-part-ii-application-2-computer-controlled-ph-gradients-in-the-presence-of-urea-provide-improved-separation-of-proteins-stability-influenced-anion-and-cation-exchange
#10
Allen G Hirsh, Latchezar I Tsonev
This paper details the use of a method of creating controlled pH gradients (pISep) to improve the separation of protein isoforms on ion exchange (IEX) stationary phases in the presence of various isocratic levels of urea. The pISep technology enables the development of computer controlled pH gradients on both cationic (CEX) and anionic (AEX) IEX stationary phases over the very wide pH range from 2 to 12. In pISep, titration curves generated by proportional mixing of the acidic and basic pISep working buffers alone, or in the presence of non-buffering solutes such as the neutral salt NaCl (0-1M), polar organics such as urea (0-8M) or acetonitrile (0-80 Vol%), can be fitted with high fidelity using high order polynomials which, in turn allows construction of a mathematical manifold %A (% acidic pISep buffer) vs...
March 16, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28342847/na-k-atpase-interaction-with-methylglyoxal-as-reactive-metabolic-side-product
#11
Marika Svrckova, Martina Zatloukalova, Petra Dvorakova, Dominika Coufalova, David Novak, Lenka Hernychova, Jan Vacek
Proteins are subject to oxidative modification and the formation of adducts with a broad spectrum of reactive species via enzymatic and non-enzymatic mechanisms. Here we report that in vitro non-enzymatic methylglyoxal (MGO) binding causes the inhibition and formation of MGO advanced glycation end-products (MAGEs) in Na(+)/K(+)-ATPase (NKA). Concretely, MGO adducts with NKA amino acid residues (mainly Arg) and N(ε)-(carboxymethyl)lysine (CML) formation were found. MGO is not only an inhibitor for solubilized NKA (IC50 = 91±16 μM), but also for reconstituted NKA in the lipid bilayer environment, which was clearly demonstrated using a DPPC/DPPE liposome model in the presence or absence of the NKA-selective inhibitor ouabain...
March 22, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28341915/in-vivo-system-for-analyzing-the-function-of-the-psbp-protein-using-chlamydomonas-reinhardtii
#12
Taishi Nishimura, Fumihiko Sato, Kentaro Ifuku
The PsbP protein is an extrinsic subunit of photosystem II (PSII) specifically developed in green-plant species including land plants and green algae. The protein-protein interactions involving PsbP and its effect on oxygen evolution have been investigated in vitro using isolated PSII membranes. However, the importance of those interactions needs to be examined at the cellular level. To this end, we developed a system expressing exogenous PsbP in the background of the Chlamydomonas BF25 mutant lacking native PsbP...
March 24, 2017: Photosynthesis Research
https://www.readbyqxmd.com/read/28341808/protein-coalation-a-redox-regulated-protein-modification-by-coenzyme-ain-mammalian-cells
#13
Yugo Tsuchiya, Sew Peak-Chew, Clare Newell, Sheritta Miller-Aidoo, Sriyash Mangal, Alexander Zhyvoloup, Jovana Baković, Oksana Malanchuk, Gonçalo Pereira, Vassilios Kotiadis, Gyorgy Szabadkai, Michael Duchen, Mark Campbell, Sergio Rodriguez Cuenca, Antonio Vidal-Puig, Andrew James, Michael P Murphy, Valeriy Filonenko, Mark Skehel, Ivan Gout
Coenzyme A (CoA) is an obligatory cofactor in all branches of life. CoA and its derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. Abnormal biosynthesis and homeostasis of CoA and its derivatives have been associated with various human pathologies, including cancer, diabetes and neurodegeneration. Using an anti-CoA monoclonal antibody and mass spectrometry we identified a wide range of cellular proteins which are modified by covalent attachment of CoA to cysteine thiols (CoAlation)...
March 24, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28341484/ruvbl1-itfg1-interaction-is-required-for-collective-invasion-in-breast-cancer
#14
Wenjun Fan, Jiajun Xie, Jianglong Xia, Yan Zhang, Mengying Yang, Hefei Wang, Yujia Pan, Mengjuan Zhang, Baochun Han, Baitong Wu, Zhijie Hou, Dapeng Liang, Chunli Wang, Jie Xu, Lijuan Song, Quentin Liu
BACKGROUND: The mechanisms of breast cancer collective invasion are poorly understood limiting the metastasis therapy. The ATPase RUVBL1 is frequently overexpressed in various cancers and plays a crucial role in oncogenic process. We further investigated the role of RUVBL1 in promoting collective invasion and uncovered that targeting RUVBL1 could inhibit metastatic progression. METHODS: The expression levels of RUVBL1 and ITFG1 were examined by Western blot and qRT-PCR...
March 21, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28340350/a-viral-immunoevasin-controls-innate-immunity-by-targeting-the-prototypical-natural-killer-cell-receptor-family
#15
Oscar A Aguilar, Richard Berry, Mir Munir A Rahim, Johanna J Reichel, Branka Popović, Miho Tanaka, Zhihui Fu, Gautham R Balaji, Timothy N H Lau, Megan M Tu, Christina L Kirkham, Ahmad Bakur Mahmoud, Aruz Mesci, Astrid Krmpotić, David S J Allan, Andrew P Makrigiannis, Stipan Jonjić, Jamie Rossjohn, James R Carlyle
Natural killer (NK) cells play a key role in innate immunity by detecting alterations in self and non-self ligands via paired NK cell receptors (NKRs). Despite identification of numerous NKR-ligand interactions, physiological ligands for the prototypical NK1.1 orphan receptor remain elusive. Here, we identify a viral ligand for the inhibitory and activating NKR-P1 (NK1.1) receptors. This murine cytomegalovirus (MCMV)-encoded protein, m12, restrains NK cell effector function by directly engaging the inhibitory NKR-P1B receptor...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28339983/acr11-is-an-activator-of-plastid-type-glutamine-synthetase-gs2-in-arabidopsis-thaliana
#16
Takashi Osanai, Ayuko Kuwahara, Hitomi Otsuki, Kazuki Saito, Masami Yokota Hirai
Glutamine synthetase (GS) is an important enzyme for nitrogen assimilation, and GS2, encoded by GLN2, is the only plastid-type GS in Arabidopsis thaliana. A co-expression analysis suggested that the expression level of the gene encoding a uridylyltransferase-like protein, ACR11, is strongly correlated with GLN2 expression levels. Here we showed that the recombinant ACR11 protein increased GS2 activity in vitro by reducing the Km values of its substrate glutamine. A T-DNA insertion mutant of ACR11 exhibited a reduced GS activity under low nitrate conditions and reduced glutamine levels...
March 6, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28339693/neuronal-signaling-repertoire-in-the-mammalian-sperm-functionality
#17
Alfredo Ramírez-Reveco, Franz Villarroel-Espíndola, Joan E Rodríguez-Gil, Ilona I Concha
The common embryonic origin has been a recurrent explanation to understand the presence of "neural receptors" in sperm. However, this designation has conditioned a bias marked by the classical neurotransmission model, dismissing the possibility that neurotransmitters can play specific roles in the sperm function by themselves. For instance, the launching of acrosome reaction, a fundamental sperm function, includes several steps that recall the process of presynaptic secretion. Unlike of postsynaptic neuron, whose activation is mediated by molecular interaction between neurotransmitter and postsynaptic receptors, the oocyte activation is not mediated by receptors, but by cytosolic translocation of sperm phospholipase (PLCζ)...
February 20, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28339215/discovery-and-pre-clinical-characterization-of-a-3-rd-generation-4-h-heteroaryldihydropyrimidine-hap-analogues-as-hepatitis-b-virus-hbv-capsid-inhibitors
#18
Zongxing Qiu, Xianfeng Lin, Weixing Zhang, Mingwei Zhou, Lei Guo, Buelent Kocer, Guolong Wu, Zhisen Zhang, Haixia Liu, Houguang Shi, Buyu Kou, Taishan Hu, Yimin Hu, Mengwei Huang, S Frank Yan, Zhiheng Xu, Zheng Zhou, Ning Qin, Yue Fen Wang, Shuang Ren, Hongxia Qiu, Yuxia Zhang, Yi Zhang, Xiaoyue Wu, Kai Sun, Sheng Zhong, Jianxun Xie, Giorgio Ottaviani, Yuan Zhou, Lina Zhu, Xiaojun Tian, Liping Shi, Fang Shen, Yi Mao, Xue Zhou, Lu Gao, John A T Young, Jim Zhen Wu, Guang Yang, Alexander V Mayweg, Hong C Shen, Guozhi Tang, Wei Zhu
Described herein are the discovery and structure-activity relationship (SAR) studies of the 3(rd) generation 4-H heteroaryldihydropyrimidines (4-H HAPs) featuring the introduction of a C6 carboxyl group as novel HBV capsid inhibitors. This new series of 4-H HAPs showed improved anti-HBV activity and better drug-like properties compared to the 1(st) and 2(nd) generation 4-H HAPs. X-ray crystallographic study of analogue 12 (HAP_R01) with Cp149 Y132A mutant hexamer clearly elucidated the role of C6 carboxyl group played for the increased binding affinity, which formed strong hydrogen bonding interactions with capsid protein and coordinated waters...
March 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28338873/molecular-dissection-of-the-actin-binding-ability-of-the-fission-yeast-%C3%AE-actinin-ain1-in-vitro-and-in-vivo
#19
Rikuri Morita, Masak Takaine, Osamu Numata, Kentaro Nakano
A contractile ring (CR) is involved in cytokinesis in animal and yeast cells. Although several types of actin-bundling proteins associate with F-actin in the CR, their individual roles in the CR have not yet been elucidated in detail. Ain1 is the sole α-actinin homologue in the fission yeast Schizosaccharomyces pombe and specifically localizes to the CR with a high turnover rate. S. pombe cells lacking the ain1+ gene show defects in cytokinesis under stress conditions. We herein investigated the biochemical activity and cellular localization mechanisms of Ain1...
February 28, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/28338815/enhanced-tenogenic-differentiation-and-tendon-like-tissue-formation-by-chip-overexpression-in-tendon-derived-stem-cells
#20
Weifeng Han, Lei Chen, Junpeng Liu, Ai Guo
The carboxyl terminus of Hsc70-interacting protein (CHIP, also known as STUB1) plays critical roles in the proliferation and differentiation of many types of cells. The potential function of CHIP in tendon-derived stem cells (TDSCs) remains largely unknown at present. Here, we investigated the effects of CHIP on tenogenic differentiation of TDSCs via lentivirus-mediated overexpression. Forced expression of CHIP induced morphological changes and significantly enhanced cell proliferation, as well as tendon differentiation in vitro...
February 22, 2017: Acta Biochimica et Biophysica Sinica
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