Monitoring Keap1–Nrf2 interactions in single live cells
| العنوان: | Monitoring Keap1–Nrf2 interactions in single live cells |
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| المؤلفون: | Sam Swift, Albena T. Dinkova-Kostova, Liam Baird, David Llères |
| المساهمون: | Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM) |
| المصدر: | Biotechnology Advances Biotechnology Advances, Elsevier, 2014, 32 (6), pp.1133-1144. ⟨10.1016/j.biotechadv.2014.03.004⟩ |
| بيانات النشر: | HAL CCSD, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | FLIM, Keap1, RBX1, [SDV]Life Sciences [q-bio], Bioengineering, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Applied Microbiology and Biotechnology, environment and public health, Nrf2, Cell Line, chemistry.chemical_compound, Mice, Fluorescence Resonance Energy Transfer, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Transcription factor, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Binding Sites, Kelch-Like ECH-Associated Protein 1, Intracellular Signaling Peptides and Proteins, Signal transducing adaptor protein, respiratory system, Cell biology, Ubiquitin ligase, Rats, Förster resonance energy transfer, chemistry, NF-E2 Transcription Factor, p45 Subunit, Isothiocyanate, Research Review Paper, biology.protein, FRET, Cytoprotective enzymes, Signal transduction, Single-Cell Analysis, Sulforaphane, Biotechnology, Signal Transduction |
| الوصف: | International audience; The transcription factor NF-E2 p45-related factor 2 (Nrf2) and its negative regulator Kelch-like ECH associated protein 1 (Keap1) control the expression of nearly 500 genes with diverse cytoprotective functions. Keap1, a substrate adaptor protein for Cullin3/Rbx1 ubiquitin ligase, normally continuously targets Nrf2 for degradation, but loses this ability in response to electrophiles and oxidants (termed inducers). Consequently, Nrf2 accumulates and activates transcription of its downstream target genes. Many inducers are phytochemicals, and cruciferous vegetables represent one of the richest sources of inducer activity among the most commonly used edible plants. Here we summarize the discovery of the isothiocyanate sulforaphane as a potent inducer which reacts with cysteine sensors of Keap1, leading to activation of Nrf2. We then describe the development of a quantitative Förster resonance energy transfer (FRET)-based methodology combined with multiphoton fluorescence lifetime imaging microscopy (FLIM) to investigate the interactions between Keap1 and Nrf2 in single live cells, and the effect of sulforaphane, and other cysteine-reactive inducers, on the dynamics of the Keap1-Nrf2 protein complex. We present the experimental evidence for the "cyclic sequential attachment and regeneration" or "conformation cycling" model of Keap1-mediated Nrf2 degradation. Finally, we discuss the implications of this mode of regulation of Nrf2 for achieving a fine balance under normal physiological conditions, and the consequences and mechanisms of disrupting this balance for tumor biology. |
| اللغة: | English |
| تدمد: | 0734-9750 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f31380384f18f256d2657d8ed42bafedTest https://hal.archives-ouvertes.fr/hal-03027057Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....f31380384f18f256d2657d8ed42bafed |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 07349750 |
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