{"doi":"10.1101/2022.03.29.486281","title":"3’UTR-directed, kinase proximal mRNA decay inhibits C/EBPβ phosphorylation/activation to suppress senescence in tumor cells","abstract":"Abstract C/EBPβ is a potent regulator of oncogene-induced senescence (OIS) and the SASP. C/EBPβ is post-translationally activated in OIS cells by the effector kinases ERK1/2 and CK2. However, in tumor cells C/EBPβ activation is suppressed by its 3’UTR. 3′UTR regulation of protein activity (UPA) requires a G/U-rich element (GRE) and its cognate binding protein, HuR. These components segregate CEBPB transcripts away from a perinuclear compartment harboring ERK1/2 and CK2, restricting C/EBPβ from its activating kinases. We report here that the mRNA decay proteins UPF1 and Staufen1/2 are essential UPA factors enriched within the perinuclear cytoplasm. STAU1/2 and UPF1 overlap with CK2 on perinuclear signaling endosomes where they promote localized CEBPB mRNA decay. UPF1 or STAU1/2 depletion in tumor cells increased CEBPB transcripts adjacent to CK2 foci, coinciding with C/EBPβ activation and senescence. The GRE and an adjacent STAU binding site independently suppress C/EBPβ-mediated senescence, while a distinct 3’UTR region inhibits its SASP-inducing activity. Kras G12D -driven lung tumors in mice carrying a Cebpb GRE deletion rarely progressed to malignant adenocarcinomas, demonstrating the importance of UPA to enable tumor progression in vivo . Thus, kinase-proximal mRNA decay is a novel mechanism that inhibits C/EBPβ activation in tumor cells to facilitate senescence bypass.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":306747,"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":0.9576,"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":1001100,"name":"Nida Asif","orcid":"0000-0001-8243-6200","position":1,"is_corresponding":false},{"id":1001101,"name":"Srikanta Basu","orcid":"0000-0002-0461-3731","position":2,"is_corresponding":false},{"id":931776,"name":"Aniruddha Das","orcid":"0000-0002-7704-3573","position":3,"is_corresponding":false},{"id":1001102,"name":"Mei Yang","orcid":"0000-0002-1784-570X","position":4,"is_corresponding":false},{"id":641691,"name":"Baktiar Karim","orcid":"0000-0001-9604-9762","position":5,"is_corresponding":false},{"id":1001437,"name":"Karen Saylor","orcid":null,"position":6,"is_corresponding":false},{"id":1001438,"name":"Nancy Martín","orcid":null,"position":7,"is_corresponding":false},{"id":583560,"name":"David A. Scheiblin","orcid":"0000-0002-5505-2540","position":8,"is_corresponding":false},{"id":1001103,"name":"Sweta Misra","orcid":"0009-0000-4902-0481","position":9,"is_corresponding":false},{"id":523887,"name":"Brian T. Luke","orcid":"0000-0002-2777-7376","position":10,"is_corresponding":false},{"id":276014,"name":"Þorkell Andrésson","orcid":"0000-0002-9545-2450","position":11,"is_corresponding":false},{"id":317886,"name":"Stephen Lockett","orcid":"0000-0002-2010-9914","position":12,"is_corresponding":false},{"id":275782,"name":"Lino Tessarollo","orcid":"0000-0001-6420-772X","position":13,"is_corresponding":false},{"id":477626,"name":"Peter F. Johnson","orcid":"0000-0002-4145-4725","position":14,"is_corresponding":false},{"id":478310,"name":"Jacqueline Salotti","orcid":null,"position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T00:32:52.703737Z","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":[]}