{"doi":"10.1016/j.celrep.2020.01.093","title":"TIFAB Regulates USP15-Mediated p53 Signaling during Stressed and Malignant Hematopoiesis","abstract":"TRAF-interacting protein with a forkhead-associated domain B (TIFAB) is implicated in myeloid malignancies with deletion of chromosome 5q. Employing a combination of proteomic and genetic approaches, we find that TIFAB regulates ubiquitin-specific peptidase 15 (USP15) ubiquitin hydrolase activity. Expression of TIFAB in hematopoietic stem/progenitor cells (HSPCs) permits USP15 signaling to substrates, including MDM2 and KEAP1, and mitigates p53 expression. Consequently, TIFAB-deficient HSPCs exhibit compromised USP15 signaling and are sensitized to hematopoietic stress by derepression of p53. In MLL-AF9 leukemia, deletion of TIFAB increases p53 signaling and correspondingly decreases leukemic cell function and development of leukemia. Restoring USP15 expression partially rescues the function of TIFAB-deficient MLL-AF9 cells. Conversely, elevated TIFAB represses p53, increases leukemic progenitor function, and correlates with MLL gene expression programs in leukemia patients. Our studies uncover a function of TIFAB as an effector of USP15 activity and rheostat of p53 signaling in stressed and malignant HSPCs.","journal":"Cell Reports","year":2020,"id":95168,"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":36,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9579,"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":467523,"name":"Kathleen Hueneman","orcid":"0000-0002-6194-3569","position":1,"is_corresponding":false},{"id":329281,"name":"Kwangmin Choi","orcid":"0000-0003-4671-962X","position":2,"is_corresponding":false},{"id":399397,"name":"Melinda E. Varney","orcid":"0000-0001-9616-4808","position":3,"is_corresponding":false},{"id":473222,"name":"Laurel Romano","orcid":"0000-0002-9597-024X","position":4,"is_corresponding":false},{"id":301665,"name":"Mario Pujato","orcid":"0000-0002-2415-3111","position":5,"is_corresponding":false},{"id":87808,"name":"Kenneth D. Greis","orcid":"0000-0002-5316-3351","position":6,"is_corresponding":false},{"id":473223,"name":"Jun‐ichiro Inoue","orcid":"0000-0001-6389-7036","position":7,"is_corresponding":false},{"id":425445,"name":"Ruhikanta A. Meetei","orcid":null,"position":8,"is_corresponding":false},{"id":467530,"name":"Daniel T. Starczynowski","orcid":"0000-0002-5771-7462","position":9,"is_corresponding":false},{"id":473221,"name":"Madeline Niederkorn","orcid":"0000-0003-1789-9078","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":null,"created_at":"2026-07-18T22:33:30.364261Z","pmid":"32101751","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":[]}