{"doi":"10.17615/36f7-nz97","title":"Fortilin potentiates the peroxidase activity of Peroxiredoxin-1 and protects against alcohol-induced liver damage in mice","abstract":"Fortilin, a pro-survival molecule, inhibits p53-induced apoptosis by binding to the sequence-specific DNA-binding domain of the tumor suppressor protein and preventing it from transcriptionally activating Bax. Intriguingly, fortilin protects cells against ROS-induced cell death, independent of p53. The signaling pathway through which fortilin protects cells against ROS-induced cell death, however, is unknown. Here we report that fortilin physically interacts with the antioxidant enzyme peroxiredoxin-1 (PRX1), protects it from proteasome-mediated degradation, and keeps it enzymatically active by blocking its deactivating phosphorylation by Mst1, a serine/threonine kinase. At the whole animal level, the liver-specific overexpression of fortilin reduced PRX1 phosphorylation in the liver, enhanced PRX1 activity, and protected the transgenic animals against alcohol-induced, ROS-mediated, liver damage. These data suggest the presence of a novel oxidative-stress-handling pathway where the anti-p53 molecule fortilin augments the peroxidase PRX1 by protecting it against degradation and inactivation of the enzyme. Fortilin-PRX1 interaction in the liver could be clinically exploited further to prevent acute alcohol-induced liver damage in humans.","journal":"Scholar Works  (Boise State University)","year":2020,"id":138600,"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":0.9441,"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":600032,"name":"Ken Fujise","orcid":"0000-0002-6763-8055","position":1,"is_corresponding":false},{"id":600033,"name":"Hung Q. Doan","orcid":"0000-0002-4715-0562","position":2,"is_corresponding":false},{"id":600034,"name":"Decha Pinkaew","orcid":"0000-0001-8334-1545","position":3,"is_corresponding":false},{"id":423866,"name":"Owen M. McDougal","orcid":"0000-0002-1502-3462","position":4,"is_corresponding":false},{"id":600654,"name":"Reed B. Jacob","orcid":null,"position":5,"is_corresponding":false},{"id":600035,"name":"Alan C. Peterson","orcid":"0000-0002-8334-8162","position":6,"is_corresponding":false},{"id":600036,"name":"Sunil Kumar Verma","orcid":"0000-0002-7460-2667","position":7,"is_corresponding":false},{"id":600037,"name":"Hana Friedman","orcid":"0000-0002-3794-5273","position":8,"is_corresponding":false},{"id":575627,"name":"Muge N. Kuyumcu‐Martinez","orcid":"0000-0003-3171-5861","position":9,"is_corresponding":false},{"id":600031,"name":"Abhijnan Chattopadhyay","orcid":"0000-0002-9907-213X","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:02.849477Z","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":[]}