{"doi":"10.1101/2020.01.11.902973","title":"An Oncometabolite Isomer Rapidly Induces A Pathophysiological Protein Modification","abstract":"ABSTRACT Metabolites regulate protein function via covalent and non-covalent interactions. However, manipulating these interactions in living cells remains a major challenge. Here we report a chemical strategy for inducing cysteine S-succination, a non-enzymatic posttranslational modification derived from the oncometabolite fumarate. Using a combination of antibody-based detection and kinetic assays we benchmark the in vitro and cellular reactivity of two novel S-succination “agonists,” maleate and 2-bromosuccinate. Cellular assays reveal maleate to be a more potent and less toxic inducer of S-succination which can activate KEAP1-NRF2 signaling in living cells. By enabling the cellular reconstitution of an oncometabolite-protein interaction with physiochemical accuracy and minimal toxicity, this study provides a methodological basis for better understanding the signaling role of metabolites in disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":128713,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9597,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":232483,"name":"Chloe A. Briney","orcid":"0000-0001-7778-9167","position":1,"is_corresponding":false},{"id":453517,"name":"Susana S. Najera","orcid":"0000-0002-3441-8013","position":2,"is_corresponding":false},{"id":453518,"name":"Minervo Perez","orcid":"0000-0002-2768-4954","position":3,"is_corresponding":false},{"id":51073,"name":"W. Marston Linehan","orcid":"0000-0001-7983-3109","position":4,"is_corresponding":false},{"id":232494,"name":"Jordan L. Meier","orcid":"0000-0002-0537-7101","position":5,"is_corresponding":false},{"id":453516,"name":"Sarah E. Bergholtz","orcid":"0009-0000-0869-4850","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T23:15:42.522809Z","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":[]}