Cao, Min, Day, Alison M, Galler, Martin, Latimer, Heather R, Byrne, Dominic P, Foy, Thomas W, Dwyer, Emilia, Bennett, Elise, Palmer, Jeremy, Morgan, Brian A et al (show 2 more authors)
(2023)
A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms.
MOLECULAR CELL, 83 (17).
3140-+.
Text
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Abstract
Peroxiredoxins (Prdxs) utilize reversibly oxidized cysteine residues to reduce peroxides and promote H<sub>2</sub>O<sub>2</sub> signal transduction, including H<sub>2</sub>O<sub>2</sub>-induced activation of P38 MAPK. Prdxs form H<sub>2</sub>O<sub>2</sub>-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 H<sub>2</sub>O<sub>2</sub>-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 H<sub>2</sub>O<sub>2</sub>-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.
Item Type: | Article |
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Uncontrolled Keywords: | Humans, Saccharomyces cerevisiae, Hydrogen Peroxide, Disulfides, Cysteine, p38 Mitogen-Activated Protein Kinases, Oxidation-Reduction, Peroxiredoxins |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
Depositing User: | Symplectic Admin |
Date Deposited: | 04 Mar 2024 09:46 |
Last Modified: | 04 Mar 2024 09:47 |
DOI: | 10.1016/j.molcel.2023.07.018 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3179036 |