{"doi":"10.17615/stec-zy85","title":"Transforming Growth Factor  /Smad3 Signaling Regulates IRF-7 Function and Transcriptional Activation of the Beta Interferon Promoter","abstract":"The rapid induction of alpha interferon (IFN-α) and IFN-β expression plays a critical role in the innate immune response against viral infection. We studied the effects of transforming growth factor β (TGF-β) and its intracellular effectors, the Smads, on the function of IRF-7, an essential transcription factor for IFN-α and -β induction. IRF-7 interacted with Smads, and IRF-7, but not IRF-3, cooperated with Smad3 to activate IFN-β transcription. This transcriptional cooperation occurred at the IRF-binding sequences in the IFN-β promoter, and dominant-negative interference with TGF-β receptor signaling and Smad3 function decreased IRF-7-mediated transcription. Furthermore, elimination of Smad3 expression in Smad3−/− fibroblasts delayed and decreased double-stranded RNA-induced expression of endogenous IFN-β, whereas restoration of Smad3 expression enhanced IFN-β induction. The IRF-7-Smad3 cooperativity resulted from the regulation of the transactivation activity of IRF-7 by Smad3, and dominant-negative interference with Smad3 function decreased IRF-7 activity. Consistent with the regulation by Smad3, the transcriptional activity of IRF-7 depended on and was regulated by TGF-β signaling. Our studies underscore a role of TGF-β/Smad3 signaling in IRF-7-mediated induction of IFN-β expression.","journal":"UNC Libraries","year":2020,"id":139067,"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":0.9588,"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":601866,"name":"Jinkang Qing","orcid":null,"position":1,"is_corresponding":false},{"id":601867,"name":"Lucas Brendan Choy","orcid":null,"position":2,"is_corresponding":false},{"id":601868,"name":"R. Derynck","orcid":null,"position":3,"is_corresponding":false},{"id":601869,"name":"R.-Y. Wu","orcid":null,"position":4,"is_corresponding":false},{"id":522903,"name":"J. S. Pagano","orcid":null,"position":5,"is_corresponding":false},{"id":601865,"name":"Changseng Liu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:06.651725Z","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":[]}