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https://www.readbyqxmd.com/read/28230851/using-hiclip-to-identify-rna-duplexes-that-interact-with-a-specific-rna-binding-protein
#1
Yoichiro Sugimoto, Anob M Chakrabarti, Nicholas M Luscombe, Jernej Ule
The structure of RNA molecules has a critical role in regulating gene expression, largely through influencing their interactions with RNA-binding proteins (RBPs). RNA hybrid and individual-nucleotide resolution UV cross-linking and immunoprecipitation (hiCLIP) is a transcriptome-wide method of monitoring these interactions by identifying RNA duplexes bound by a specific RBP. The hiCLIP protocol consists of the following steps: in vivo cross-linking of RBPs to their bound RNAs; partial RNA digestion and purification of RNA duplexes interacting with the specific RBP using immunoprecipitation; ligation of the two arms of RNA duplexes via a linker; reverse transcription; cDNA library amplification; and finally high-throughput DNA sequencing...
March 2017: Nature Protocols
https://www.readbyqxmd.com/read/28225045/membrane-targeting-of-tirap-is-negatively-regulated-by-phosphorylation-in-its-phosphoinositide-binding-motif
#2
Xiaolin Zhao, Wen Xiong, Shuyan Xiao, Tuo-Xian Tang, Jeffrey F Ellena, Geoffrey S Armstrong, Carla V Finkielstein, Daniel G S Capelluto
Pathogen-activated Toll-like receptors (TLRs), such as TLR2 and TLR4, dimerize and move laterally across the plasma membrane to phosphatidylinositol (4,5)-bisphosphate-enriched domains. At these sites, TLRs interact with the TIR domain-containing adaptor protein (TIRAP), triggering a signaling cascade that leads to innate immune responses. Membrane recruitment of TIRAP is mediated by its phosphoinositide (PI)-binding motif (PBM). We show that TIRAP PBM transitions from a disordered to a helical conformation in the presence of either zwitterionic micelles or monodispersed PIs...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224988/post-endocytic-sorting-of-plexin-d1-controls-signal-transduction-and-development-of-axonal-and-vascular-circuits
#3
Katja Burk, Erik Mire, Anaïs Bellon, Mélanie Hocine, Jeremy Guillot, Filipa Moraes, Yutaka Yoshida, Michael Simons, Sophie Chauvet, Fanny Mann
Local endocytic events involving receptors for axon guidance cues play a central role in controlling growth cone behaviour. Yet, little is known about the fate of internalized receptors, and whether the sorting events directing them to distinct endosomal pathways control guidance decisions. Here, we show that the receptor Plexin-D1 contains a sorting motif that interacts with the adaptor protein GIPC1 to facilitate transport to recycling endosomes. This sorting process promotes colocalization of Plexin-D1 with vesicular pools of active R-ras, leading to its inactivation...
February 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28223944/il-1%C3%AE-induced-downregulation-of-the-multifunctional-pdz-adaptor-pdzk1-is-attenuated-by-erk-inhibition-rxr%C3%AE-or-ppar%C3%AE-stimulation-in-enterocytes
#4
Min Luo, Sunil Yeruva, Yongjian Liu, Giriprakash Chodisetti, Brigitte Riederer, Manoj B Menon, Keisuke Tachibana, Takefumi Doi, Ursula E Seidler
Background: The PDZ adaptor protein PDZK1 modulates the membrane expression and function of a variety of intestinal receptors and ion/nutrient transporters. Its expression is strongly decreased in inflamed intestinal mucosa of mice and IBD patients. Aim and Methods: We investigated whether the inflammation-associated PDZK1 downregulation is a direct consequence of proinflammatory cytokine release by treating intestinal Caco-2BBE cells with TNF-α, IFN-γ, and IL-1β, and analysing PDZK1 promotor activity, mRNA and protein expression...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28222762/the-hippo-component-yap-localizes-in-the-nucleus-of-human-papilloma-virus-positive-oropharyngeal-squamous-cell-carcinoma
#5
Faisal Alzahrani, Leanne Clattenburg, Shanmugam Muruganandan, Martin Bullock, Kaitlyn MacIsaac, Michael Wigerius, Blair A Williams, M Elise R Graham, Matthew H Rigby, Jonathan R B Trites, S Mark Taylor, Christopher J Sinal, James P Fawcett, Robert D Hart
BACKGROUND: HPV infection causes cervical cancer, mediated in part by the degradation of Scribble via the HPV E6 oncoprotein. Recently, Scribble has been shown to be an important regulator of the Hippo signaling cascade. Deregulation of the Hippo pathway induces an abnormal cellular transformation, epithelial to mesenchymal transition, which promotes oncogenic progression. Given the recent rise in oropharyngeal HPV squamous cell carcinoma we sought to determine if Hippo signaling components are implicated in oropharyngeal squamous cell carcinoma...
February 22, 2017: Journal of Otolaryngology—Head & Neck Surgery
https://www.readbyqxmd.com/read/28222108/oxidative-stress-mediated-nf%C3%AE%C2%BAb-phosphorylation-upregulates-p62-sqstm1-and-promotes-retinal-pigmented-epithelial-cell-survival-through-increased-autophagy
#6
Chunjuan Song, Sayak K Mitter, Xiaoping Qi, Eleni Beli, Haripriya V Rao, Jindong Ding, Colin S Ip, Hongmei Gu, Debra Akin, William A Dunn, Catherine Bowes Rickman, Alfred S Lewin, Maria B Grant, Michael E Boulton
p62 is a scaffolding adaptor implicated in the clearance of protein aggregates by autophagy. Reactive oxygen species (ROS) can either stimulate or inhibit NFκB-mediated gene expression influencing cellular fate. We studied the effect of hydrogen peroxide (H2O2)-mediated oxidative stress and NFκB signaling on p62 expression in the retinal pigment epithelium (RPE) and investigated its role in regulation of autophagy and RPE survival against oxidative damage. Cultured human RPE cell line ARPE-19 and primary human adult and fetal RPE cells were exposed to H2O2-induced oxidative stress...
2017: PloS One
https://www.readbyqxmd.com/read/28220498/the-role-of-apical-cell-cell-junctions-and-associated-cytoskeleton-in-mechanotransduction
#7
REVIEW
Sophie Sluysmans, Ekaterina Vasileva, Domenica Spadaro, Jimit Shah, Florian Rouaud, Sandra Citi
Tissues of multicellular organisms are characterized by several types of specialized cell-cell junctions. In vertebrate epithelia and endothelia, tight and adherens junctions play critical roles in barrier and adhesion functions, and are connected to the actin and microtubule cytoskeletons. The interaction between junctions and the cytoskeleton is crucial for tissue development and physiology, and is involved in the molecular mechanisms governing cell shape, motility, growth and signaling. The machineries which functionally connect tight and adherens junctions to the cytoskeleton comprise proteins which either bind directly to cytoskeletal filaments, or function as adaptors for regulators of the assembly and function of the cytoskeleton...
February 21, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/28220253/myd88-in-mycobacterium-tuberculosis-infection
#8
EDITORIAL
Jorge L Cervantes
MyD88 adaptor protein mediates numerous biologically important signal transduction pathways in innate immunity. MyD88 signaling fosters bacterial containment and is necessary to raise an adequate innate and acquired immune response to Mycobacterium tuberculosis (Mtb). The phagosome is a crucial cellular location not only for Mtb replication, but it is also where components of the Myddosome and inflammasome are recruited. Besides its function as a TLR-adaptor protein, MyD88 may help stabilizing cytosolic receptors that are recruited to the phagosome...
February 20, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28216678/the-cul3-spop-daxx-axis-is-a-novel-regulator-of-vegfr2-expression-in-vascular-endothelial-cells
#9
Tomohisa Sakaue, Iori Sakakibara, Takahiro Uesugi, Ayako Fujisaki, Koh-Ichi Nakashiro, Hiroyuki Hamakawa, Eiji Kubota, Takashi Joh, Yu-Ki Imai, Hironori Izutani, Shigeki Higashiyama
Vascular endothelial cell growth factor receptor 2 (VEGFR2) is an essential receptor for the homeostasis of endothelial cells. In this study, we showed that NEDD8-conjugated Cullin3 (CUL3)-based ubiquitin E3 (UbE3) ligase plays a crucial role in VEGFR2 mRNA expression. Human umbilical vein endothelial cells treated with MLN4924, an inhibitor of NEDD8-activating enzyme, or with CUL3 siRNA drastically lost their response to VEGF due to the intense decrease in VEGFR2 expression. Moreover, speckle-type POZ protein (SPOP) and death-domain associated protein (DAXX) were involved in the CUL3 UbE3 ligase complex as a substrate adaptor and a substrate, respectively...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28215293/neuronal-roles-of-the-bicaudal-d-family-of-motor-adaptors
#10
M Budzinska, K B Wicher, M Terenzio
All cell types rely on active intracellular cargo transport to shuttle essential cellular components such as proteins, lipids, RNA, and even organelles from the center to the periphery and vice versa. Additionally, several signaling pathways take advantage of intracellular transport to propagate their signals by moving activated receptors and protein effectors to specific locations inside the cell. Neurons particularly, being a very polarized cell type, are highly dependent on molecular motors for the anterograde and retrograde delivery of essential cellular components and signaling molecules...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28215140/position-based-nucleotide-analysis-of-mir168-family-in-higher-plants-and-its-targets-in-mammalian-transcripts
#11
Mohammed Javed, Manish Solanki, Anshika Sinha, Lata Israni Shukla
The conserved miR168 family is evaluated for position based nucleotide preference in higher plants. The mature miRNA sequences include miR168-5p and miR168-3p, were obtained from miRBase (v21, June 2014) for 15 families (28 plants) containing a-c subfamilies. The preferred position based nucleotide sequences were obtained for miR168-5p and miR168-3p using Data Analysis in Molecular Biology and Evolution (DAMBE). miR168-5p shows same nucleotides at positions 1-6, 8-9, 11-12, 15-17 and 19. Also, miR168-3p is present in 3 families (10 plants) shows the same nucleotide at position 1-11, 13-15 and 17-21...
February 15, 2017: MicroRNA
https://www.readbyqxmd.com/read/28214847/contribution-of-p62-to-phenotype-transition-of-coronary-arterial-myocytes-with-defective-autophagy
#12
Junxiang Bao, Guangbi Li, Xinxu Yuan, Erich Gulbins, Pin-Lan Li
BACKGROUND: Autophagy disorder contributes to dedifferentiation of arterial smooth muscle cells, but the mechanisms are poorly understood. Here, we sought to investigate the role of scaffolding adaptor p62/SQSTM1 (p62) in phenotype switching of mouse coronary arterial myocytes (CAMs) induced by CD38 gene deficiency or lysosomal dysfunction which blocks autophagic flux in the cells. METHODS: Protein expression was measured by western blot analysis and immunofluorescent staining...
3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28213521/signalling-adaptor-shcd-suppresses-erk-phosphorylation-distal-to-the-ret-and-trk-neurotrophic-receptors
#13
Melanie K B Wills, Ava Keyvani Chahi, Hayley R Lau, Manali Tilak, Brianna Guild, Laura A New, Peihua Lu, Keévin Jacquet, Susan O Meakin, Nicolas Bisson, Nina Jones
Proteins of the Shc family are typically involved in signal transduction events involving Ras/MAPK and PI3K/Akt pathways. In the nervous system, they function proximal to the neurotrophic factors that regulate cell survival, differentiation, and neuron-specific characteristics. The least-characterized homolog, ShcD, is robustly expressed in the developing and mature nervous system, but its contributions to neural cell circuitry are largely uncharted. We now report that ShcD binds to active Ret, TrkA, and TrkB neurotrophic factor receptors predominantly via its phosphotyrosine binding (PTB) domain...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28211872/rictor-mtorc2-deficiency-enhances-keratinocyte-stress-tolerance-via-mitohormesis
#14
Beatrice Tassone, Stefania Saoncella, Francesco Neri, Ugo Ala, Davide Brusa, Mark A Magnuson, Paolo Provero, Salvatore Oliviero, Chiara Riganti, Enzo Calautti
How metabolic pathways required for epidermal tissue growth and remodeling influence the ability of keratinocytes to survive stressful conditions is still largely unknown. The mechanistic target of rapamycin complex 2 (mTORC2) regulates growth and metabolism of several tissues, but its functions in epidermal cells are poorly defined. Rictor is an adaptor protein essential for mTORC2 activity. To explore the roles of mTORC2 in the epidermis, we have conditionally deleted rictor in mice via K14-Cre-mediated homologous recombination and found that its deficiency causes moderate tissue hypoplasia, reduced keratinocyte proliferation and attenuated hyperplastic response to TPA...
February 17, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28209562/vinexin-%C3%AE-ablation-inhibits-atherosclerosis-in-apolipoprotein-e-deficient-mice-by-inactivating-the-akt-nuclear-factor-%C3%AE%C2%BAb-inflammatory-axis
#15
Hongjing Guan, Wen-Lin Cheng, Junhong Guo, Meng-Lin Chao, Yan Zhang, Jun Gong, Xue-Yong Zhu, Zhi-Gang She, Zan Huang, Hongliang Li
BACKGROUND: Vinexin β is a novel adaptor protein that regulates cellular adhesion, cytoskeletal reorganization, signal transduction, and transcription; however, the exact role that vinexin β plays in atherosclerosis remains unknown. METHODS AND RESULTS: Immunoblot analysis showed that vinexin β expression is upregulated in the atherosclerotic lesions of both patients with coronary heart disease and hyperlipemic apolipoprotein E-deficient mice and is primarily localized in macrophages indicated by immunofluorescence staining...
February 16, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28202760/restriction-of-hcmv-replication-by-isg15-a-host-effector-regulated-by-cgas-sting-dsdna-sensing
#16
Christopher Bianco, Ian Mohr
Accumulation of the interferon-stimulated gene (ISG) 15 protein product, which is reversibly conjugated to numerous polypeptide targets, impacts the proteome and physiology of uninfected and infected cells. While many viruses, including human cytomegalovirus (HCMV) blunt host antiviral defenses by limiting ISG expression, the overall abundance of ISG15 monomer and protein conjugates rises in HCMV-infected cells. However, the molecular signals underlying ISG15 accumulation and whether the ISG15 polypeptide itself influences HCMV infection biology remain unknown...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28199188/trigonella-seed-extract-ameliorates-inflammation-via-regulation-of-the-inflammasome-adaptor-protein-asc
#17
Nidhi Sharma, Samyuktha Suresh, Ananya Debnath, Sushmita Jha
Trigonella foenum-graecum (fenugreek) is an important medicinal plant, well known for its anti-inflammatory properties. However, the underlying cellular and molecular mechanisms of its action remain largely unknown. The apoptosis associated speck like protein containing a caspase recruitment domain (CARD) (ASC) is central to inflammatory and cell death pathways in innate and adaptive immunity. Here, we show that fenugreek seed extract provides cytoprotection to bacterial lipopolysaccharide (LPS) inflammed and nanosilica-treated fibroblasts via a reactive oxygen species independent pathway...
March 1, 2017: Frontiers in Bioscience (Elite Edition)
https://www.readbyqxmd.com/read/28198500/molecular-characterization-expression-and-functional-analysis-of-chicken-traf6
#18
J Jin, J S Ran, C W Yang, X S Jiang, Y G Zhou, Z Q Feng, Y Wang, D Lan, P Ren, Y P Liu
Tumor necrosis factor receptor-associated factor 6 (TRAF6) is a crucial adaptor molecule of the interleukin-1 receptor/Toll-like receptor (IL-1/TLR) superfamily, which can trigger downstream signaling cascades involved in innate immunity. The function of TRAF6 has been clarified in mammals but is poorly understood in chicken. In our study, we investigated TRAF6 function in birds, particularly in chicken innate immune responses, by cloning and characterizing chicken TRAF6 (chTRAF6). The full-length coding sequence of chTRAF6 comprised 1638 bp and encoded a 545-amino acid protein, which shares high sequence similarity with TRAF6 of other species and consists of four structurally conserved domains...
February 8, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28195158/infection-derived-lipids-elicit-an-immune-deficiency-circuit-in-arthropods
#19
Dana K Shaw, Xiaowei Wang, Lindsey J Brown, Adela S Oliva Chávez, Kathryn E Reif, Alexis A Smith, Alison J Scott, Erin E McClure, Vishant M Boradia, Holly L Hammond, Eric J Sundberg, Greg A Snyder, Lei Liu, Kathleen DePonte, Margarita Villar, Massaro W Ueti, José de la Fuente, Robert K Ernst, Utpal Pal, Erol Fikrig, Joao H F Pedra
The insect immune deficiency (IMD) pathway resembles the tumour necrosis factor receptor network in mammals and senses diaminopimelic-type peptidoglycans present in Gram-negative bacteria. Whether unidentified chemical moieties activate the IMD signalling cascade remains unknown. Here, we show that infection-derived lipids 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG) and 1-palmitoyl-2-oleoyl diacylglycerol (PODAG) stimulate the IMD pathway of ticks. The tick IMD network protects against colonization by three distinct bacteria, that is the Lyme disease spirochete Borrelia burgdorferi and the rickettsial agents Anaplasma phagocytophilum and A...
February 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28192730/inducible-turnover-of-optineurin-regulates-t-cell-activation
#20
Angela Montecalvo, Simon C Watkins, Jordan Orange, Lawrence P Kane
Optineurin (Optn) is an adaptor protein with homology to NF-κB essential modulator (NEMO), the regulatory subunit of the IκB kinase (IKK) complex. Dysregulation of Optn has been linked to neurodegenerative, autoimmune and bone diseases. Optn shares a high degree of homology with NEMO, but is not part of the same high-molecular weight complex containing IKKα and IKKβ. Despite its homology with NEMO and the fact that it has been the subject of extensive study in several cell types, there are no published studies addressing the role of Optn during T cell activation...
February 10, 2017: Molecular Immunology
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