A functionally defined high-density NRF2 interactome reveals new conditional regulators of ARE transactivation.

Binary interactome Dual luminescence-based co-immunoprecipitation (DULIP) Fluorescence cross-correlation spectroscopy (FCCS) Human disease network KEAP1 NRF2/NFE2L2 Protein interaction network (PIN)

Journal

Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639

Informations de publication

Date de publication:
10 2020
Historique:
received: 20 05 2020
revised: 02 08 2020
accepted: 12 08 2020
pubmed: 11 9 2020
medline: 25 5 2021
entrez: 10 9 2020
Statut: ppublish

Résumé

NRF2 (NFE2L2) is a cytoprotective transcription factor associated with >60 human diseases, adverse drug reactions and therapeutic resistance. To provide insight into the complex regulation of NRF2 responses, 1962 predicted NRF2-partner interactions were systematically tested to generate an experimentally defined high-density human NRF2 interactome. Verification and conditional stratification of 46 new NRF2 partners was achieved by co-immunoprecipitation and the novel integration of quantitative data from dual luminescence-based co-immunoprecipitation (DULIP) assays and live-cell fluorescence cross-correlation spectroscopy (FCCS). The functional impact of new partners was then assessed in genetically edited loss-of-function (NRF2

Identifiants

pubmed: 32911434
pii: S2213-2317(20)30891-0
doi: 10.1016/j.redox.2020.101686
pmc: PMC7490560
pii:
doi:

Substances chimiques

Kelch-Like ECH-Associated Protein 1 0
NF-E2-Related Factor 2 0
NFE2L2 protein, human 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

101686

Subventions

Organisme : Medical Research Council
ID : MR/K015931/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 102172/Z/13/Z
Pays : United Kingdom

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

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Auteurs

Jonathan Poh (J)

Institute of Translational Medicine, University of Liverpool, UK.

Amy H Ponsford (AH)

Institute of Translational Medicine, University of Liverpool, UK.

James Boyd (J)

Institute of Translational Medicine, University of Liverpool, UK.

Jonathan Woodsmith (J)

Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Austria.

Ulrich Stelzl (U)

Institute of Pharmaceutical Sciences, Department of Pharmaceutical Chemistry, University of Graz, Austria.

Erich Wanker (E)

Max-Delbrück Center for Molecular Medicine (MDC), Berlin-Buch, Germany.

Nicholas Harper (N)

Institute of Translational Medicine, University of Liverpool, UK.

David MacEwan (D)

Institute of Translational Medicine, University of Liverpool, UK.

Christopher M Sanderson (CM)

Institute of Translational Medicine, University of Liverpool, UK. Electronic address: cmsand@liverpool.ac.uk.

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Classifications MeSH