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In vivo protein protein interaction

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https://www.readbyqxmd.com/read/29144726/physalis-mottle-virus-like-particles-as-nanocarriers-for-imaging-reagents-and-drugs
#1
Hema Masarapu, Bindi K Patel, Paul L Chariou, He Hu, Neetu M Gulati, Bradley L Carpenter, Reza A Ghiladi, Sourabh Shukla, Nicole F Steinmetz
Platform technologies based on plant virus nanoparticles (VNPs) and virus-like particles (VLPs) are attracting the attention of researchers and clinicians because the particles are biocompatible, biodegradable, noninfectious in mammals, and can readily be chemically and genetically engineered to carry imaging agents and drugs. When the Physalis mottle virus (PhMV) coat protein is expressed in Escherichia coli, the resulting VLPs are nearly identical to the viruses formed in vivo. Here, we isolated PhMV-derived VLPs from ClearColi cells and carried out external and internal surface modification with fluorophores using reactive lysine-N-hydroxysuccinimide ester and cysteine-maleimide chemistries, respectively...
November 16, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29144441/g-protein-coupled-receptors-targeted-by-analgesic-venom-peptides
#2
REVIEW
James T Daniel, Richard J Clark
Chronic pain is a complex and debilitating condition associated with a large personal and socioeconomic burden. Current pharmacological approaches to treating chronic pain such as opioids, antidepressants and anticonvulsants exhibit limited efficacy in many patients and are associated with dose-limiting side effects that hinder their clinical use. Therefore, improved strategies for the pharmacological treatment of pathological pain are urgently needed. G-protein coupled receptors (GPCRs) are ubiquitously expressed on the surface of cells and act to transduce extracellular signals and regulate physiological processes...
November 16, 2017: Toxins
https://www.readbyqxmd.com/read/29143419/long-non-coding-rna-rp11-380d23-2-drives-distal-proximal-patterning-of-the-lung-by-regulating-pitx2-expression
#3
Poulomi Banerjee, Harshini Surendran, Kapil Bharti, Kaoru Morishita, Anurag Varshney, Rajarshi Pal
Early lung development is a tightly orchestrated process encompassing (a) formation of definitive endoderm, (b) anteriorization of definitive endoderm followed by (c) specification and maturation of both proximal and distal lung precursors. Several reports detailing the interaction of genes and proteins during lung development are available; however, studies reporting the role(s) of long non-coding RNAs (lncRNA) in lung morphogenesis are limited. To investigate this, we tailored a protocol for differentiation of human induced pluripotent stem cells into distal and proximal lung progenitors to mimic in vivo lung development...
November 16, 2017: Stem Cells
https://www.readbyqxmd.com/read/29142129/entry-of-human-coronavirus-nl63-to-the-cell
#4
Aleksandra Milewska, Paulina Nowak, Katarzyna Owczarek, Artur Szczepanski, Miroslaw Zarebski, Agnieszka Hoang-Bujnowicz, Krzysztof Berniak, Jacek Wojarski, Slawomir Zeglen, Zbigniew Baster, Zenon Rajfur, Krzysztof Pyrc
First steps of human coronavirus NL63 (HCoV-NL63) infection were previously described. The virus binds to target cells by heparan sulfate proteoglycans, and interacts with the ACE2 protein. Subsequent events, including virus internalization and trafficking, remain to be elucidated. In this study, we mapped the process of HCoV-NL63 entry into LLC-Mk2 cell line and ex vivo 3D tracheobronchial tissue.Using a variety of techniques we have shown that HCoV-NL63 virions require endocytosis for successful entry to the LLC-MK2 cells, and interaction between the virus and the ACE2 molecule triggers recruitment of clathrin...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29142068/pharmacologic-inhibition-of-the-menin-mll-interaction-leads-to-transcriptional-repression-of-peg10-and-blocks-hepatocellular-carcinoma
#5
Katarzyna Kempinska, Bhavna Malik, Dmitry Borkin, Szymon Klossowski, Shirish Shukla, Hongzhi Miao, Jingya Wang, Tomasz Cierpicki, Jolanta Grembecka
Hepatocellular carcinoma (HCC) accounts for ~85% of malignant liver tumors and results in 600,000 deaths each year, emphasizing the need for new therapies. Upregulation of menin was reported in HCC patients and high levels of menin correlate with poor patient prognosis. The protein-protein interaction between menin and histone methyltransferase Mixed Lineage Leukemia 1 (MLL1) plays an important role in the development of HCC, implying that pharmacologic inhibition of this interaction could lead to new therapeutic strategy for the HCC patients...
November 15, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29140585/timap-the-versatile-protein-phosphatase-1-regulator-in-endothelial-cells
#6
REVIEW
Anita Boratkó, Csilla Csortos
Transforming growth factor (TGF)-β inhibited membrane associated protein, TIMAP, is the member of the myosin phosphatase targeting protein (MYPT) family of protein phosphatase 1 (PP1) regulatory subunits. The N-terminal part of TIMAP has a typical MYPT family structure with a sequence element called MyPhone (myosin phosphatase N-terminal element), a putative bipartite nuclear localization signal, a PP1 catalytic subunit binding motif, and five ankyrin repeats. The C-terminal half of TIMAP is intrinsically disordered, but ends with a functional CAAX box for lipid modification which allows localization of TIMAP at the plasma membrane...
November 15, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29140461/a-bacterial-three-hybrid-assay-detects-escherichia-coli-hfq-srna-interactions-in-vivo
#7
Katherine E Berry, Ann Hochschild
The interaction of RNA molecules with proteins is a critical aspect of gene regulation across all domains of life. Here, we report the development of a bacterial three-hybrid (B3H) assay to genetically detect RNA-protein interactions. The basis for this three-hybrid assay is a transcription-based bacterial two-hybrid assay that has been used widely to detect and dissect protein-protein interactions. In the three-hybrid assay, a DNA-bound protein with a fused RNA-binding moiety (the coat protein of bacteriophage MS2 (MS2CP)) is used to recruit a hybrid RNA upstream of a test promoter...
November 11, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29138497/rapid-purification-of-human-bispecific-antibodies-via-selective-modulation-of-protein-a-binding
#8
Adam Zwolak, Catherine N Leettola, Susan H Tam, Dennis R Goulet, Mehabaw G Derebe, Jose R Pardinas, Songmao Zheng, Rose Decker, Eva Emmell, Mark L Chiu
Methods to rapidly generate high quality bispecific antibodies (BsAb) having normal half-lives are critical for therapeutic programs. Here, we identify 3 mutations (T307P, L309Q, and Q311R or "TLQ") in the Fc region of human IgG1 which disrupt interaction with protein A while enhancing interaction with FcRn. The mutations are shown to incrementally alter the pH at which a mAb elutes from protein A affinity resin. A BsAb comprised of a TLQ mutant and a wild-type IgG1 can be efficiently separated from contaminating parental mAbs by differential protein A elution starting from either a) purified parental mAbs, b) in-supernatant crossed parental mAbs, or c) co-transfected mAbs...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137415/ubiquitin-conjugating-enzyme-e2-l3-promoted-tumor-growth-of-nsclc-through-accelerating-p27kip1-ubiquitination-and-degradation
#9
Xingjie Ma, Junjie Zhao, Fan Yang, Haitao Liu, Weibo Qi
The molecular pathogenesis of human lung cancer has not been completely clarified. Here, we reported that UBE2L3, a member of the ubiquitin-conjugating enzymes (E2s), were overexpressed in non-small-cell lung cancer (NSCLC) tissues compared with the non-tumor tissues. High expression of UBE2L3 was correlated with advanced tumor stage and adverse outcomes. Knockdown of UBE2L3 inhibited NSCLC cell growth while ectopic expression of UBE2L3 promoted NSCLC cell growth in a cell cycle dependent manner. The results of subcutaneous tumor xenograft studies revealed that knockdown of UBE2L3 attenuated the in vivo tumor growth...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137386/mitochondrial-calcium-uniporter-as-a-target-of-microrna-340-and-promoter-of-metastasis-via-enhancing-the-warburg-effect
#10
Changhui Yu, Yuhao Wang, Jiawen Peng, Qiang Shen, Mimi Chen, Wei Tang, Xiumei Li, Chunqing Cai, Bin Wang, Shaoxi Cai, Xiaojing Meng, Fei Zou
Background: A shift from oxygen phosphorylation to aerobic glycolysis was known as the Warburg effect and a characteristic of cancer cell metabolism facilitating metastasis. Mitochondrial calcium uniporter (MCU), a key ion channel that mediates Ca(2+) uptake into mitochondria, was found to promote cancer progression and metastasis. However, its explicit role in shifting metabolism of breast cancer cells has not been defined. Methods: We evaluated MCU overexpression or knock-down on migration, invasion and glucose metabolismin breast cancer cells...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136249/natural-polyphenol-chlorogenic-acid-protects-against-acetaminophen-induced-hepatotoxicity-by-activating-erk-nrf2-antioxidative-pathway
#11
Mengjuan Wei, Zhiyong Zheng, Liang Shi, Yao Jin, Lili Ji
Hepatotoxicity due to acetaminophen (APAP) overdose is a leading cause of drug-induced acute liver failure in clinic. Chlorogenic acid (CGA), a dietary polyphenol, was reported to prevent APAP-induced liver injury in our previous studies. This study aims to investigate the protection provided by CGA against APAP-induced hepatotoxicity via focusing on nuclear factor erythroid 2-related factor 2 (Nrf2) and extracellular regulated protein kinases (ERK)1/2. CGA prevented APAP-induced oxidative liver injury and enhanced Nrf2 activation in mice and in hepatocytes in vitro...
November 10, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29134727/a-srna-in-a-reduced-mutualistic-symbiont-genome-regulates-its-own-gene-expression
#12
Margaret W Thairu, Siyuan Cheng, Allison K Hansen
Similar to other nutritional endosymbionts that are obligate for host survival, the mutualistic aphid endosymbiont, Buchnera, has a highly reduced genome with few regulatory elements. Until recently, it was thought that aphid hosts were primarily responsible for regulating their symbiotic relationship. However, we recently revealed that Buchnera displays differential protein regulation, but not mRNA expression. We also identified a number of conserved small RNAs (sRNAs) that are expressed among Buchnera taxa...
November 13, 2017: Molecular Ecology
https://www.readbyqxmd.com/read/29133853/dispersion-of-tio2-nanoparticles-improves-burn-wound-healing-and-tissue-regeneration-through-specific-interaction-with-blood-serum-proteins
#13
Gulaim A Seisenbaeva, Karin Fromell, Vasiliy V Vinogradov, Aleksey N Terekhov, Andrey V Pakhomov, Bo Nilsson, Kristina Nilsson Ekdahl, Vladimir V Vinogradov, Vadim G Kessler
Burn wounds are one of the most important causes of mortality and especially morbidity around the world. Burn wound healing and skin tissue regeneration remain thus one of the most important challenges facing the mankind. In the present study we have addressed this challenge, applying a solution-stabilized dispersion TiO2 nanoparticles, hypothesizing that their ability to adsorb proteins will render them a strong capacity in inducing body fluid coagulation and create a protective hybrid material coating. The in vitro study of interaction between human blood and titania resulted at enhanced TiO2 concentrations in formation of rather dense gel composite materials and even at lower content revealed specific adsorption pattern initiating the cascade response, promising to facilitate the regrowth of the skin...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133832/jmjd8-is-a-novel-endoplasmic-reticulum-protein-with-a-jmjc-domain
#14
Kok Siong Yeo, Ming Cheang Tan, Yat-Yuen Lim, Chee-Kwee Ea
Jumonji C (JmjC) domain-containing proteins have been shown to regulate cellular processes by hydroxylating or demethylating histone and non-histone targets. JMJD8 belongs to the JmjC domain-only family that was recently shown to be involved in angiogenesis and TNF-induced NF-κB signaling. Here, we employed bioinformatic analysis and immunofluorescence microscopy to examine the physiological properties of JMJD8. We demonstrated that JMJD8 localizes to the lumen of endoplasmic reticulum and that JMJD8 forms dimers or oligomers in vivo...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133573/the-rars-mad1l1-fusion-gene-induces-cancer-stem-cell-like-properties-and-therapeutic-resistance-in-nasopharyngeal-carcinoma
#15
Qian Zhong, Zhihua Liu, Zhi-Rui Lin, Ze-Dong Hu, Li Yuan, Yan-Min Liu, Ai-Jun Zhou, Li-Hua Xu, Li-Juan Hu, Zi-Feng Wang, Xin Yuan Guan, Jia-Jie Hao, Vivian Wai Yan Lui, Ling Guo, Hai-Qiang Mai, Ming-Yuan Chen, Fei Han, Yun-Fei Xia, Jennifer R Grandis, Xing Zhang, Mu-Sheng Zeng
PURPOSE: Nasopharyngeal carcinoma (NPC) is most common head and neck cancer in Southeast Asia. Because local recurrence and distant metastasis are still the main causes of NPC treatment failure, it is urgent to identify new tumor markers and therapeutic targets for advanced NPC. EXPERIMENTAL DESIGN: RNA-seq was applied to look for interchromosome translocation in NPC. PCR, FISH and immunoprecipitation were used to examine the fusion gene expression at RNA, DNA, and protein levels in NPC biopsies...
November 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29133369/transcription-factor-wrky75-interacts-with-della-proteins-to-affect-flowering
#16
Ligang Chen, Liping Zhang, Diqiu Yu
Flowering time is tightly controlled by both endogenous and exogenous signals. Although several lines of evidence have suggested the involvement of WRKY transcription factors in floral initiation, the underlying mechanisms and signaling pathways involved remain elusive. Here, we newly identified Arabidopsis thaliana WRKY DNA binding protein75 (WRKY75) as a positive regulator of flowering initiation. Mutation of WRKY75 resulted in a delay in flowering, whereas overexpression of WRKY75 significantly accelerated flowering in Arabidopsis...
November 13, 2017: Plant Physiology
https://www.readbyqxmd.com/read/29133306/quaking-inhibits-doxorubicin-mediated-cardiotoxicity-through-regulation-of-cardiac-circular-rna-expression
#17
Shashi K Gupta, Ankita Garg, Christian Bär, Shambhabi Chatterjee, Ariana Foinquinos, Hendrik Milting, Katrin Streckfuss-Bömeke, Jan Fiedler, Thomas Thum
Rationale: RNA-binding proteins (RBPs) have been described to be expressed and regulated in various organs including the heart. Little is known about the role of RBPs in heart failure induced by the chemotherapy drug doxorubicin and their interaction with circular RNAs. Objective: We aimed to identify key RBPs involved in doxorubicin-mediated heart failure and to elucidate their function. Methods and Results: Global transcriptome profiling from murine myocardium exposed to doxorubicin identified five differentially expressed RBPs...
November 13, 2017: Circulation Research
https://www.readbyqxmd.com/read/29133205/hpma-copolymer-conjugate-with-pirarubicin-in-vitro-and-ex-vivo-stability-and-drug-release-study
#18
Waliul Islam, Jun Fang, Tomas Etrych, Petr Chytil, Karel Ulbrich, Akihiro Sakoguchi, Katsuki Kusakabe, Hiroshi Maeda
We have developed a tumor environment-responsive polymeric anticancer prodrug containing pirarubicin (THP) conjugated to N-(2-hydroxypropyl) methacrylamide copolymer (PHPMA), [P-THP], through a spacer containing pH-sensitive hydrazone bond, that showed remarkable therapeutic effect against various tumor models and in a human pilot study. Toward clinical development, here we report THP release profile from its HPMA copolymer conjugate, the conjugate stability, protein and cell-binding and solubility of P-THP...
November 10, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29132026/integrated-omics-analysis-of-root-preferred-genes-across-diverse-rice-varieties-including-japonica-and-indica-cultivars
#19
Sunok Moon, Anil Kumar Nalini Chandran, Yun-Shil Gho, Sun-A Park, Sung-Ryul Kim, Yo-Han Yoo, Ki-Hong Jung
Plant root systems play essential roles in developmental processes, such as the absorption of water and inorganic nutrients, and structural support. Gene expression is affected by growth conditions and the genetic background of plants. To identify highly conserved root-preferred genes in rice across diverse growth conditions and varieties, we used two independent meta-anatomical expression profiles based on a large collection of Affymetrix and Agilent 44K microarray data sets available for public use. We then identified 684 loci with root-preferred expression, which were validated with in silico analysis using both meta-expression profiles...
October 26, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/29130686/thioamide-substitution-selectively-modulates-proteolysis-and-receptor-activity-of-therapeutic-peptide-hormones
#20
Xing Chen, Elizabeth G Mietlicki-Baase, Taylor M Barrett, Lauren E McGrath, Kieran Koch-Laskowski, John J Ferrie, Matthew R Hayes, E James Petersson
Peptide hormones are attractive as injectable therapeutics and imaging agents, but they often require extensive modification by mutagenesis and/or chemical synthesis to prevent rapid in vivo degradation. Alternatively, the single-atom, O-to-S modification of peptide backbone thioamidation has the potential to selectively perturb interactions with proteases while preserving interactions with other proteins, such as target receptors. Here, we use the validated diabetes therapeutic, glucagon-like peptide-1 (GLP-1), and the target of clinical investigation, gastric inhibitory polypeptide (GIP), as proof-of-principle peptides to demonstrate the value of thioamide substitution...
November 13, 2017: Journal of the American Chemical Society
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