{"doi":"10.1101/2022.11.15.513554","title":"A Peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms","abstract":"Summary Peroxiredoxins (Prdx) utilize reversibly oxidized cysteine residues to reduce peroxides but also to promote H 2 O 2 signal transduction, including H 2 O 2 -induced activation of P38 MAPK. Prdx form H 2 O 2 -induced disulfide complexes with many proteins, including multiple kinases involved in P38 MAPK signaling. Here we show that a genetically-encoded fusion between Prdx and the P38 MAPK is sufficient to hyperactivate the kinase in yeast and human cells by a mechanism that does not require the H 2 O 2 -sensing cysteine of the Prdx. In yeast, we demonstrate that a P38-Prdx fusion protein compensates for the loss of a scaffold protein and upstream MAP3K kinase activity, driving entry into mitosis. Based on our findings, we propose that the H 2 O 2 -induced formation of Prdx-MAPK disulfide complexes provides a scaffold and signaling platform for MAPKK-MAPK signaling. The demonstration that formation of a complex with a Prdx can be sufficient to modify the activity of a kinase has broad implications for peroxide-based signal transduction in eukaryotes. Highlights P38-Prdx complexes increase P38 (Sty1/MAPK14) phosphorylation in yeast and human cells The S. pombe Prdx promotes transient thioredoxin-mediated oxidation of a MAPK tyrosine phosphatase P38-Prdx complexes increase P38(Sty1) activity by phosphatase and MAP3K-independent mechanisms P38-Prdx complexes increase the stability and phosphorylation of the S. pombe P38 MAPKK (Wis1) Non-canonical, H 2 O 2 -induced autophosphorylation contributes to activation of the Wis1 MAPKK","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":298436,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":987885,"name":"Alison M. Day","orcid":null,"position":1,"is_corresponding":false},{"id":274581,"name":"Martin Galler","orcid":"0000-0001-5668-3857","position":2,"is_corresponding":false},{"id":987886,"name":"Heather Latimer","orcid":null,"position":3,"is_corresponding":false},{"id":274579,"name":"Dominic P. Byrne","orcid":"0000-0001-5197-345X","position":4,"is_corresponding":false},{"id":987887,"name":"Emilia Dwyer","orcid":null,"position":5,"is_corresponding":false},{"id":987888,"name":"Elise Bennett","orcid":null,"position":6,"is_corresponding":false},{"id":274588,"name":"Patrick A. Eyers","orcid":"0000-0002-9220-2966","position":7,"is_corresponding":false},{"id":274586,"name":"Elizabeth A. Veal","orcid":"0000-0002-1152-5473","position":8,"is_corresponding":false},{"id":274582,"name":"Min Cao","orcid":"0000-0001-6199-7797","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T00:31:36.269611Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}