{"doi":"10.15252/embr.202255472","title":"p38 MAPK‐dependent phosphorylation of TFEB promotes monocyte‐to‐macrophage differentiation","abstract":"The transcription factor EB (TFEB) regulates energy homeostasis and cellular response to a wide variety of stress conditions, including nutrient deprivation, oxidative stress, organelle damage, and pathogens. Here we identify S401 as a novel phosphorylation site within the TFEB proline-rich domain. Phosphorylation of S401 increases significantly in response to oxidative stress, UVC light, growth factors, and LPS, whereas this increase is prevented by p38 MAPK inhibition or depletion, revealing a new role for p38 MAPK in TFEB regulation. Mutation of S401 in THP1 cells demonstrates that the p38 MAPK/TFEB pathway plays a particularly relevant role during monocyte differentiation into macrophages. TFEB-S401A monocytes fail to upregulate the expression of multiple immune genes in response to PMA-induced differentiation, including critical cytokines, chemokines, and growth factors. Polarization of M0 macrophages into M1 inflammatory macrophages is also aberrant in TFEB-S401A cells. These results indicate that TFEB-S401 phosphorylation links differentiation signals to the transcriptional control of monocyte differentiation.","journal":"EMBO Reports","year":2022,"id":243460,"datarank":1.0584823155729546,"base_score":3.5553480614894135,"endowment":3.5553480614894135,"self_citation_contribution":0.5333022092234121,"citation_network_contribution":0.5251801063495425,"self_endowment_contribution":0.5333022092234121,"citer_contribution":0.5251801063495425,"corpus_percentile":null,"corpus_rank":null,"citation_count":34,"citer_count":32,"citers_with_citation_signal":20,"citers_with_endowment":20,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":true,"deposit_databanks":{"GEO":["GSE201826","GSE217608"]},"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":639254,"name":"Eutteum Jeong","orcid":null,"position":1,"is_corresponding":false},{"id":263646,"name":"Rosa Puertollano","orcid":"0000-0002-1106-5489","position":2,"is_corresponding":false},{"id":331603,"name":"José A. Martina","orcid":"0000-0001-5814-8807","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T00:23:16.032700Z","pmid":"36507874","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":[]}