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https://www.readbyqxmd.com/read/28338015/simultaneously-measuring-multiple-protein-interactions-and-their-correlations-in-a-cell-by-protein-interactome-footprinting
#1
Si-Wei Luo, Zhi Liang, Jia-Rui Wu
Quantitatively detecting correlations of multiple protein-protein interactions (PPIs) in vivo is a big challenge. Here we introduce a novel method, termed Protein-interactome Footprinting (PiF), to simultaneously measure multiple PPIs in one cell. The principle of PiF is that each target physical PPI in the interactome is simultaneously transcoded into a specific DNA sequence based on dimerization of the target proteins fused with DNA-binding domains. The interaction intensity of each target protein is quantified as the copy number of the specific DNA sequences bound by each fusion protein dimers...
March 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28334977/sclip-an-integrated-platform-to-study-rna-protein-interactomes-in-biomedical-research-identification-of-cstf2tau-in-alternative-processing-of-small-nuclear-rnas
#2
Yulia Kargapolova, Michal Levin, Karl Lackner, Sven Danckwardt
RNA-binding proteins (RBPs) are central for gene expression by controlling the RNA fate from birth to decay. Various disorders arising from perturbations of RNA-protein interactions document their critical function. However, deciphering their function is complex, limiting the general functional elucidation of this growing class of proteins and their contribution to (patho)physiology. Here, we present sCLIP, a simplified and robust platform for genome-wide interrogation of RNA-protein interactomes based on crosslinking-immunoprecipitation and high-throughput sequencing...
February 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28333928/network-perturbation-by-recurrent-regulatory-variants-in-cancer
#3
Kiwon Jang, Kwoneel Kim, Ara Cho, Insuk Lee, Jung Kyoon Choi
Cancer driving genes have been identified as recurrently affected by variants that alter protein-coding sequences. However, a majority of cancer variants arise in noncoding regions, and some of them are thought to play a critical role through transcriptional perturbation. Here we identified putative transcriptional driver genes based on combinatorial variant recurrence in cis-regulatory regions. The identified genes showed high connectivity in the cancer type-specific transcription regulatory network, with high outdegree and many downstream genes, highlighting their causative role during tumorigenesis...
March 23, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28332981/global-reorganisation-of-cis-regulatory-units-upon-lineage-commitment-of-human-embryonic-stem-cells
#4
Paula Freire-Pritchett, Stefan Schoenfelder, Csilla Várnai, Steven W Wingett, Jonathan Cairns, Amanda J Collier, Raquel García-Vílchez, Mayra Furlan-Magaril, Cameron S Osborne, Peter J Fraser, Peter J Rugg-Gunn, Mikhail Spivakov
Long-range cis-regulatory elements such as enhancers coordinate cell-specific transcriptional programmes by engaging in DNA looping interactions with target promoters. Deciphering the interplay between the promoter connectivity and activity of cis-regulatory elements during lineage commitment is crucial for understanding developmental transcriptional control. Here, we use Promoter Capture Hi-C to generate a high-resolution atlas of chromosomal interactions involving ~22,000 gene promoters in human pluripotent and lineage-committed cells, identifying putative target genes for known and predicted enhancer elements...
March 23, 2017: ELife
https://www.readbyqxmd.com/read/28332498/a-genome-wide-screen-identifies-yap-wbp2-interplay-conferring-growth-advantage-on-human-epidermal-stem-cells
#5
Gernot Walko, Samuel Woodhouse, Angela Oliveira Pisco, Emanuel Rognoni, Kifayathullah Liakath-Ali, Beate M Lichtenberger, Ajay Mishra, Stephanie B Telerman, Priyalakshmi Viswanathan, Meike Logtenberg, Lisa M Renz, Giacomo Donati, Sven R Quist, Fiona M Watt
Individual human epidermal cells differ in their self-renewal ability. To uncover the molecular basis for this heterogeneity, we performed genome-wide pooled RNA interference screens and identified genes conferring a clonal growth advantage on normal and neoplastic (cutaneous squamous cell carcinoma, cSCC) human epidermal cells. The Hippo effector YAP was amongst the top positive growth regulators in both screens. By integrating the Hippo network interactome with our data sets, we identify WW-binding protein 2 (WBP2) as an important co-factor of YAP that enhances YAP/TEAD-mediated gene transcription...
March 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28331560/introducing-crucial-protein-panel-of-gastric-adenocarcinoma-disease
#6
Mostafa Rezaei-Tavirani, Majid Rezaei-Tavirani, Vahid Mansouri, Seyed Mohammad Mahdavi, Reza Valizadeh, Mohammad Rostami-Nejad, Mohammad Reza Zali
AIM: Since interactome analysis of diseases can provide candidate biomarker panel related to the diseases, in this research, protein-protein interaction (PPI) network analysis is used to introduce the involved crucial proteins in Gastric adenocarcinoma (GA). BACKGROUND: Gastric adenocarcinoma (GA) is the most common type of stomach cancer. There is no efficient diagnostic molecular method for GA. METHOD: Applying Cytoscape software 3.4.0 and String Database, the PPI network was constructed for 200 genes...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28330929/the-role-of-pias-sumo-e3-ligases-in-cancer
#7
REVIEW
Andrea Rabellino, Cristina Andreani, Pier Paolo Scaglioni
SUMOylation modifies the interactome, localization, activity, and lifespan of its target proteins. This process regulates several cellular machineries, including transcription, DNA damage repair, cell-cycle progression, and apoptosis. Accordingly, SUMOylation is critical in maintaining cellular homeostasis, and its deregulation leads to the corruption of a plethora of cellular processes that contribute to disease states. Among the proteins involved in SUMOylation, the protein inhibitor of activated STAT (PIAS) E3-ligases were initially described as transcriptional coregulators...
March 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28330605/polyubiquitin-photoactivatable-crosslinking-reagents-for-mapping-ubiquitin-interactome-identify-rpn1-as-a-proteasome-ubiquitin-associating-subunit
#8
Michal Chojnacki, Wissam Mansour, Dharjath S Hameed, Rajesh K Singh, Farid El Oualid, Rina Rosenzweig, Mark A Nakasone, Zanlin Yu, Fabian Glaser, Lewis E Kay, David Fushman, Huib Ovaa, Michael H Glickman
Ubiquitin (Ub) signaling is a diverse group of processes controlled by covalent attachment of small protein Ub and polyUb chains to a range of cellular protein targets. The best documented Ub signaling pathway is the one that delivers polyUb proteins to the 26S proteasome for degradation. However, studies of molecular interactions involved in this process have been hampered by the transient and hydrophobic nature of these interactions and the lack of tools to study them. Here, we develop Ub-phototrap (Ub(PT)), a synthetic Ub variant containing a photoactivatable crosslinking side chain...
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28324507/using-protein-fragment-complementation-assays-pca-and-peptide-arrays-to-study-telomeric-protein-protein-interactions
#9
Wenbin Ma, Ok-Hee Lee, Hyeung Kim, Zhou Songyang
Studying protein-protein interactions is critical to our understanding of signaling pathways. Telomere Interactome is assembled around telomeres and consists of proteins and factors from diverse pathways. Dissecting how this protein network contributes to telomere protection and length regulation requires the elucidation of the complex and dynamic interactions between the proteins within the interactome. Here, we focus on three assays, Bi-molecular Fluorescence Complementation (BiFC), Gaussia Luciferase Protein-fragment Complementation Assay (GLuc PCA), and OPAL peptide array, which have proven vital in our studies of telomere protein interaction networks...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28321204/a-comprehensive-view-of-the-%C3%AE-arrestinome
#10
Pascale Crépieux, Anne Poupon, Nathalie Langonné-Gallay, Eric Reiter, Javier Delgado, Martin H Schaefer, Thomas Bourquard, Luis Serrano, Christina Kiel
G protein-coupled receptors (GPCRs) are membrane receptors critically involved in sensing the environment and orchestrating physiological processes. As such, they transduce extracellular signals such as hormone, neurotransmitters, ions, and light into an integrated cell response. The intracellular trafficking, internalization, and signaling ability of ligand-activated GPCRs are controlled by arrestins, adaptor proteins that they interact with upon ligand binding. β-arrestins 1 and 2 in particular are now considered as hub proteins assembling multiprotein complexes to regulate receptor fate and transduce diversified cell responses...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28314116/secretory-proteome-analysis-of-streptomycin-resistant-mycobacterium-tuberculosis-clinical-isolates
#11
Divakar Sharma, Deepa Bisht
Tuberculosis still remains one of the most fatal infectious diseases. Streptomycin (SM) is the drug of choice, especially for patients with multidrug-resistant tuberculosis or category II patients, because it targets the protein synthesis machinery by interacting with steps of translation. Several mechanisms have been proposed to explain the resistance, but our knowledge is inadequate. Secretome often plays an important role in pathogenesis and is considered an attractive reservoir for the development of novel diagnostic markers and targets...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28298427/systematic-protein-protein-interaction-mapping-for-clinically-relevant-human-gpcrs
#12
Kate Sokolina, Saranya Kittanakom, Jamie Snider, Max Kotlyar, Pascal Maurice, Jorge Gandía, Abla Benleulmi-Chaachoua, Kenjiro Tadagaki, Atsuro Oishi, Victoria Wong, Ramy H Malty, Viktor Deineko, Hiroyuki Aoki, Shahreen Amin, Zhong Yao, Xavier Morató, David Otasek, Hiroyuki Kobayashi, Javier Menendez, Daniel Auerbach, Stephane Angers, Natasa Pržulj, Michel Bouvier, Mohan Babu, Francisco Ciruela, Ralf Jockers, Igor Jurisica, Igor Stagljar
G-protein-coupled receptors (GPCRs) are the largest family of integral membrane receptors with key roles in regulating signaling pathways targeted by therapeutics, but are difficult to study using existing proteomics technologies due to their complex biochemical features. To obtain a global view of GPCR-mediated signaling and to identify novel components of their pathways, we used a modified membrane yeast two-hybrid (MYTH) approach and identified interacting partners for 48 selected full-length human ligand-unoccupied GPCRs in their native membrane environment...
March 15, 2017: Molecular Systems Biology
https://www.readbyqxmd.com/read/28298180/bacterial-protein-meta-interactomes-predict-cross-species-interactions-and-protein-function
#13
J Harry Caufield, Christopher Wimble, Semarjit Shary, Stefan Wuchty, Peter Uetz
BACKGROUND: Protein-protein interactions (PPIs) can offer compelling evidence for protein function, especially when viewed in the context of proteome-wide interactomes. Bacteria have been popular subjects of interactome studies: more than six different bacterial species have been the subjects of comprehensive interactome studies while several more have had substantial segments of their proteomes screened for interactions. The protein interactomes of several bacterial species have been completed, including several from prominent human pathogens...
March 16, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28293890/characterizing-dynamic-protein-protein-interactions-using-the-genetically-encoded-split-biosensor-assay-technique-split-tev
#14
Jan P Wintgens, Moritz J Rossner, Michael C Wehr
Dynamic protein-protein interactions (PPIs) are fundamental building blocks of cellular signaling and monitoring their regulation promotes the understanding of signaling in health and disease. Genetically encoded split protein biosensor assays, such as the split TEV method, have proved to be highly valuable when studying regulated PPIs in living cells. Split TEV is based on the functional complementation of two previously inactive TEV protease fragments fused to interacting proteins and provides a robust, sensitive and flexible readout to monitor PPIs both at the membrane and in the cytosol...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28292708/dioscorea-alata-tuber-proteome-analysis-shows-over-thirty-dioscorin-isoforms-and-novel-tuber-proteins
#15
Shruti Sharma, Ravi Gupta, Renu Deswal
In Dioscorea, dioscorin (31 kDa) is the major storage protein constituting 85% of the total tuber proteins. An integrated proteomic and biochemical approach was used to understand the physiological role of dioscorin in the two contrasting growth stages (germinating and mature tuber). HPLC analysis showed 3 fold reduction in mannitol and 12.88 and 1.24 fold increase in sucrose and maltose in the germinating tuber. A 1.8 and 3 fold increase in sucrose phosphate synthase and mannitol dehydrogenase activity respectively was observed in the germinating tuber while a 2 fold higher invertase probably lowers the sucrose accumulation in the mature tuber...
March 6, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28285986/calcium-dependent-regulation-of-protein-ubiquitination-interplay-between-e3-ligases-and-calcium-binding-proteins
#16
REVIEW
Rukmini Mukherjee, Aneesha Das, Saikat Chakrabarti, Oishee Chakrabarti
The ubiquitination status of proteins and intracellular calcium levels are two factors which keep changing inside any living cell. These two events appear to be independent of each other but recent experimental evidences show that ubiquitination of cellular proteins are influenced by calcium, Calmodulin, Calmodulin-dependent kinase II and other proteins of calcium dependent pathways. E3 ligases like Nedd4, SCF complex, APC, GP78 and ITCH are important regulators of calcium mediated processes. A bioinformatics analysis to inspect sequences and interacting partners of 242 candidate E3 ligases show the presence of calcium and/or Calmodulin binding motifs/domains within their sequences...
March 7, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28284537/proteome-scale-human-interactomics
#17
REVIEW
Katja Luck, Gloria M Sheynkman, Ivy Zhang, Marc Vidal
Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites. A thorough understanding of cellular organization requires accurate and relatively complete models of interactome networks at proteome scale. The recent publication of four human protein-protein interaction (PPI) maps represents a technological breakthrough and an unprecedented resource for the scientific community, heralding a new era of proteome-scale human interactomics...
March 8, 2017: Trends in Biochemical Sciences
https://www.readbyqxmd.com/read/28280605/next-generation-sequencing-identifies-interactome-signatures-in-relapsed-and-refractory-metastatic-colorectal-cancer
#18
Benny Johnson, Laurence Cooke, Daruka Mahadevan
BACKGROUND: In the management of metastatic colorectal cancer (mCRC), KRAS, NRAS and BRAF mutational status individualizes therapeutic options and identify a cohort of patients (pts) with an aggressive clinical course. We hypothesized that relapsed and refractory mCRC pts develop unique mutational signatures that may guide therapy, predict for a response and highlight key signaling pathways important for clinical decision making. METHODS: Relapsed and refractory mCRC pts (N=32) were molecularly profiled utilizing commercially available next generation sequencing (NGS) platforms...
February 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28279225/allogenic-adipose-derived-stem-cell-therapy-overcomes-ischemia-induced-microvessel-rarefaction-in-the-myocardium-systems-biology-study
#19
Gemma Vilahur, Blanca Oñate, Judit Cubedo, Maria Teresa Béjar, Gemma Arderiu, Esther Peña, Laura Casaní, Manuel Gutiérrez, Antoni Capdevila, Guillem Pons-Lladó, Francesc Carreras, Alberto Hidalgo, Lina Badimon
BACKGROUND: Myocardial microvascular loss after myocardial infarction (MI) remains a therapeutic challenge. Autologous stem cell therapy was considered as an alternative; however, it has shown modest benefits due to the impairing effects of cardiovascular risk factors on stem cells. Allogenic adipose-derived stem cells (ASCs) may overcome such limitations, and because of their low immunogenicity and paracrine potential may be good candidates for cell therapy. In the present study we investigated the effects of allogenic ASCs and their released products on cardiac rarefaction post MI...
March 9, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28276505/alternative-exon-skipping-biases-substrate-preference-of-the-deubiquitylase-usp15-for-mysterin-rnf213-the-moyamoya-disease-susceptibility-factor
#20
Yuri Kotani, Daisuke Morito, Kenshiro Sakata, Shiori Ainuki, Munechika Sugihara, Tomohisa Hatta, Shun-Ichiro Iemura, Seiji Takashima, Tohru Natsume, Kazuhiro Nagata
The deubiquitylating enzyme USP15 plays significant roles in multiple cellular pathways including TGF-β signaling, RNA splicing, and innate immunity. Evolutionarily conserved skipping of exon 7 occurs during transcription of the mRNAs encoding USP15 and its paralogue USP4, yielding two major isoforms for each gene. Exon 7 of USP15 encodes a serine-rich stretch of 29 amino acid residues located in the inter-region linker that connects the N-terminal putative regulatory region and the C-terminal enzymatic region...
March 9, 2017: Scientific Reports
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