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Journal article
HSF1-Dependent Upregulation of Hsp70 by Sulfhydryl-Reactive Inducers of the KEAP1/NRF2/ARE Pathway
Chemistry & biology, v 18(11), pp 1355-1361
23 Nov 2011
PMID: 22118669
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The KEAP1/NRF2/ARE pathway and the heat shock response are inducible cytoprotective systems regulated by transcription factors NRF2 and HSF1, respectively. We report that structurally distinct small molecule NRF2 activators, all of which react with sulfhydryl groups but differ in potency by 15,000-fold, upregulate Hsp70, a prototypic HSF1-dependent gene. Hsp70 upregulation requires HSF1 but is NRF2 independent. We further demonstrate that a sulfoxythiocarbamate inducer conjugates to the negative regulator of HSF1, Hsp90. The differential concentration dependence of the two responses suggests that activation of NRF2 precedes that of HSF1: the KEAP1/NRF2/ARE pathway is at the forefront of cellular defense, protecting against instant danger; the heat shock response closely follows to resolve subsequent potentially devastating damage, saving the proteome. This uncovered duality undoubtedly contributes to the cytoprotective effects of such molecules in models of carcinogenesis, cardiovascular disease, and neurodegeneration.
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Details
- Title
- HSF1-Dependent Upregulation of Hsp70 by Sulfhydryl-Reactive Inducers of the KEAP1/NRF2/ARE Pathway
- Creators
- Ying Zhang - University of DundeeYoung-Hoon Ahn - Johns Hopkins UniversityIvor J. Benjamin - University of UtahTadashi Honda - Stony Brook UniversityRonald J. Hicks - California State University, East BayVittorio Calabrese - University of CataniaPhilip A. Cole - Johns Hopkins UniversityAlbena T. Dinkova-Kostova - Johns Hopkins Medicine
- Publication Details
- Chemistry & biology, v 18(11), pp 1355-1361
- Publisher
- Elsevier
- Number of pages
- 7
- Grant note
- U54RR020839 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) U54 RR020839 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA C20953/A10270 / Cancer Research UK Research Councils UK; UK Research & Innovation (UKRI) 10270 / Cancer Research UK
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Arts and Sciences; Chemistry; Drexel University
- Web of Science ID
- WOS:000297603600007
- Scopus ID
- 2-s2.0-82255181180
- Other Identifier
- 991020100060304721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology