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A protein-protein interaction map of the TNF-induced NF-κB signal transduction pathway.

Emmy Van Quickelberghe | Delphine De Sutter | Geert van Loo | Sven Eyckerman | Kris Gevaert
Scientific data | 2018

Tumor Necrosis Factor (TNF) has a crucial role in inflammation, cell proliferation and cell death. Dysregulation of TNF receptor 1 (TNFR1)-induced Nuclear Factor-kappa B (NF-κB) signaling leads to chronic inflammation and is associated with several human inflammatory pathologies. Hence, TNF neutralization suppresses inflammation and attenuates inflammatory pathology. However, despite its beneficial effects, anti-TNF therapy suffers from efficacy issues and severe immune side effects. There is thus an urging need to identify novel targets for pharmaceutical intervention in the NF-κB signaling pathway. Here, we present a protein-protein interaction dataset of the TNFR1-induced signaling pathway. For this, we used Virotrap, a novel method for studying protein complexes without disrupting the cellular integrity, on 12 central proteins controlling NF-κB and cell death signaling, both under resting conditions as well as upon TNF stimulation. Our dataset reveals dynamic interactions in TNFR1-induced NF-κB signaling and identifies both known as well as novel interactors that may help to further unravel the molecular mechanisms steering TNF-induced inflammatory signaling and pathology.

Pubmed ID: 30561431

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Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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IMEx - The International Molecular Exchange Consortium (tool)

RRID:SCR_002805

Interaction database from international collaboration between major public interaction data providers who share curation effort and develop set of curation rules when capturing data from both directly deposited interaction data or from publications in peer reviewed journals. Performs complete curation of all protein-protein interactions experimentally demonstrated within publication and makes them available in single search interface on common website. Provides data in standards compliant download formats. IMEx partners produce their own separate resources, which range from all encompassing molecular interaction databases, such as are maintained by IntAct, MINT and DIP, organism-centric resources such as BioGrid or MPIDB or biological domain centric, such as MatrixDB. They have committed to making records available, via PSICQUIC webservice, which have been curated to IMEx rules and are available to users as single, non-redundant set of curated publications which can be searched at the IMEx website. Data is made available in standards-compliant tab-deliminated and XML formats, enabling to visualize data using wide range of tools. Consortium is open to participation of additional partners and encourages deposition of data, prior to publication, and will supply unique accession numbers which may be referenced within final article. Submitters may send their data directly to any of member databases using variety of formats, but should conform to guidelines as to minimum information required to describe data.

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RRID:SCR_004055

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RRID:SCR_006944

Open source database system and analysis tools for molecular interaction data. All interactions are derived from literature curation or direct user submissions. Direct user submissions of molecular interaction data are encouraged, which may be deposited prior to publication in a peer-reviewed journal. The IntAct Database contains (Jun. 2014): * 447368 Interactions * 33021 experiments * 12698 publications * 82745 Interactors IntAct provides a two-tiered view of the interaction data. The search interface allows the user to iteratively develop complex queries, exploiting the detailed annotation with hierarchical controlled vocabularies. Results are provided at any stage in a simplified, tabular view. Specialized views then allows "zooming in" on the full annotation of interactions, interactors and their properties. IntAct source code and data are freely available.

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Randomized controlled trial being conducted at two clinical centers in the United States to learn more about the effects of weight loss on urinary incontinence. About 330 overweight women aged 30 or older will participate and will be followed for 18 months. Efficacy of weight reduction as a treatment for urinary incontinence will be examined at 6 months following the intensive weight control program, and the sustained impact of the intervention will be examined at 18 months. To increase the maintenance of weight reduction and facilitate evaluation of the enduring impact of weight loss on urinary incontinence, they propose to study a motivation-based weight maintenance program. At the end of the intensive weight control program, women randomized to the weight loss program will be randomized to either a 12-month skill-based maintenance intervention or to a motivation-based maintenance intervention. The maintenance interventions maximize the potential for sustained weight loss and will allow them to determine if long-term weight reduction will produce continued improvement in urinary incontinence.

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