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Lookup NU author(s): Dr Min Cao, Dr Alison DayORCiD, Dr Martin GallerORCiD, Heather Latimer, Tom Foy, Emilia Dwyer, Elise McDonald, Dr Jeremy PalmerORCiD, Emeritus Professor Brian Morgan, Dr Elizabeth VealORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023. Peroxiredoxins (Prdxs) utilize reversibly oxidized cysteine residues to reduce peroxides and promote H2O2 signal transduction, including H2O2-induced activation of P38 MAPK. Prdxs form H2O2-induced disulfide complexes with many proteins, including multiple kinases involved in P38 MAPK signaling. Here, we show that a genetically encoded fusion between a Prdx and P38 MAPK is sufficient to hyperactivate the kinase in yeast and human cells by a mechanism that does not require the H2O2-sensing cysteine of the Prdx. We demonstrate that a P38-Prdx fusion protein compensates for loss of the yeast scaffold protein Mcs4 and MAP3K activity, driving yeast into mitosis. Based on our findings, we propose that the H2O2-induced formation of Prdx-MAPK disulfide complexes provides an alternative scaffold and signaling platform for MAPKK-MAPK signaling. The demonstration that formation of a complex with a Prdx is sufficient to modify the activity of a kinase has broad implications for peroxide-based signal transduction in eukaryotes.
Author(s): Cao M, Day AM, Galler M, Latimer HR, Byrne DP, Foy TW, Dwyer E, Bennett E, Palmer J, Morgan BA, Eyers PA, Veal EA
Publication type: Article
Publication status: Published
Journal: Molecular Cell
Year: 2023
Volume: 83
Issue: 17
Pages: 3140-3154.e7
Print publication date: 07/09/2023
Online publication date: 11/08/2023
Acceptance date: 14/07/2023
Date deposited: 03/09/2025
ISSN (print): 1097-2765
ISSN (electronic): 1097-4164
Publisher: Cell Press
URL: https://doi.org/10.1016/j.molcel.2023.07.018
DOI: 10.1016/j.molcel.2023.07.018
Data Access Statement: All blots and microscopy images have been deposited at Mendeley Data and are publicly available as of the date of publication. DOI is listed in the key resources table. This paper does not report any original code. Any additional information required to re-analyze the data reported in this paper is available from the lead contact upon request.
PubMed id: 37572670
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