{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["10(9)"],"submitter":["Wu Q"],"pubmed_abstract":["Cytosolic double-stranded DNA surveillance by cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) signaling triggers cellular senescence, autophagy, biased mRNA translation, and interferon-mediated immune responses. However, detailed mechanisms and physiological relevance of STING-induced senescence are not fully understood. Here, we unexpectedly found that interferon regulatory factor 3 (IRF3), activated during innate DNA sensing, forms substantial endogenous complexes in the nucleus with retinoblastoma (RB), a key cell cycle regulator. The IRF3-RB interaction attenuates cyclin-dependent kinase 4/6 (CDK4/6)-mediated RB hyperphosphorylation that mobilizes RB to deactivate E2 family (E2F) transcription factors, thereby driving cells into senescence. STING-IRF3-RB signaling plays a notable role in hepatic stellate cells (HSCs) within various murine models, pushing activated HSCs toward senescence. Accordingly, IRF3 global knockout or conditional deletion in HSCs aggravated liver fibrosis, a process mitigated by the CDK4/6 inhibitor. These findings underscore a straightforward yet vital mechanism of cGAS-STING signaling in inducing cellular senescence and unveil its unexpected biology in limiting liver fibrosis."],"journal":["Science advances"],"pagination":["eadj2102"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10901380"],"repository":["biostudies-literature"],"pubmed_title":["IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis."],"pmcid":["PMC10901380"],"pubmed_authors":["Liang T","Shen L","Zhang D","Xu P","Wu Q","Zhou R","Lin X","Liu S","Zhang Q","Liu Y","Lin A","Feng XH","Mei C","Leng X","Zhu YZ","Wang X","Xia B","Chen S"],"additional_accession":[]},"is_claimable":false,"name":"IRF3 activates RB to authorize cGAS-STING-induced senescence and mitigate liver fibrosis.","description":"Cytosolic double-stranded DNA surveillance by cyclic GMP-AMP synthase (cGAS)-Stimulator of Interferon Genes (STING) signaling triggers cellular senescence, autophagy, biased mRNA translation, and interferon-mediated immune responses. However, detailed mechanisms and physiological relevance of STING-induced senescence are not fully understood. Here, we unexpectedly found that interferon regulatory factor 3 (IRF3), activated during innate DNA sensing, forms substantial endogenous complexes in the nucleus with retinoblastoma (RB), a key cell cycle regulator. The IRF3-RB interaction attenuates cyclin-dependent kinase 4/6 (CDK4/6)-mediated RB hyperphosphorylation that mobilizes RB to deactivate E2 family (E2F) transcription factors, thereby driving cells into senescence. STING-IRF3-RB signaling plays a notable role in hepatic stellate cells (HSCs) within various murine models, pushing activated HSCs toward senescence. Accordingly, IRF3 global knockout or conditional deletion in HSCs aggravated liver fibrosis, a process mitigated by the CDK4/6 inhibitor. These findings underscore a straightforward yet vital mechanism of cGAS-STING signaling in inducing cellular senescence and unveil its unexpected biology in limiting liver fibrosis.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2026-07-02T03:19:01.432Z","creation":"2025-04-05T21:48:40.026Z"},"accession":"S-EPMC10901380","cross_references":{"pubmed":["38416816"],"doi":["10.1126/sciadv.adj2102"]}}