{"doi":"10.1016/j.celrep.2023.112007","title":"The Integrator complex desensitizes cellular response to TGF-β/BMP signaling","abstract":"Maintenance of stem cells requires the concerted actions of niche-derived signals and stem cell-intrinsic factors. Although Decapentaplegic (Dpp), a Drosophila bone morphogenetic protein (BMP) molecule, can act as a long-range morphogen, its function is spatially limited to the germline stem cell niche in the germarium. We show here that Integrator, a complex known to be involved in RNA polymerase II (RNAPII)-mediated transcriptional regulation in the nucleus, promotes germline differentiation by restricting niche-derived Dpp/BMP activity in the cytoplasm. Further results show that Integrator works in various developmental contexts to desensitize the cellular response to Dpp/BMP signaling during Drosophila development. Mechanistically, our results show that Integrator forms a multi-subunit complex with the type I receptor Thickveins (Tkv) and other Dpp/BMP signaling components and acts in a negative feedback loop to promote Tkv turnover independent of its transcriptional activity. Similarly, human Integrator subunits bind transforming growth factor β (TGF-β)/BMP signaling components and antagonize their activity, suggesting a conserved role of Integrator across metazoans.","journal":"Cell Reports","year":2023,"id":335850,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9447,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1065836,"name":"Gyeong Hun Baeg","orcid":"0000-0002-3307-0924","position":1,"is_corresponding":false},{"id":678096,"name":"Ying Yang","orcid":"0000-0002-2032-9183","position":2,"is_corresponding":false},{"id":725366,"name":"Feng Guang Goh","orcid":"0000-0001-6189-0877","position":3,"is_corresponding":false},{"id":682989,"name":"Hongcun Bao","orcid":null,"position":4,"is_corresponding":false},{"id":250364,"name":"Eric J. Wagner","orcid":"0000-0003-0217-383X","position":5,"is_corresponding":false},{"id":72358,"name":"Xiaohang Yang","orcid":"0000-0001-5192-5706","position":6,"is_corresponding":false},{"id":725368,"name":"Yu Cai","orcid":"0000-0003-2044-3290","position":7,"is_corresponding":false},{"id":640457,"name":"Sen Liu","orcid":"0000-0001-5182-7241","position":0,"is_corresponding":true}],"reference_count":121,"raw_metadata":null,"created_at":"2026-07-19T01:10:02.777338Z","pmid":"36641752","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":[]}