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- W4223544904 abstract "Article11 April 2022 Source DataTransparent process CDK inhibitor Palbociclib targets STING to alleviate autoinflammation Jiani Gao Jiani Gao Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Validation, Writing - original draft, Writing - review & editing Search for more papers by this author Mengge Zheng Mengge Zheng Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Validation, Writing - original draft, Writing - review & editing Search for more papers by this author Xiangyang Wu Xiangyang Wu orcid.org/0000-0002-0444-7120 Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Validation, Writing - original draft, Writing - review & editing Search for more papers by this author Hang Zhang Hang Zhang orcid.org/0000-0001-9485-5883 Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai, China Contribution: Software Search for more papers by this author Hang Su Hang Su Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Software Search for more papers by this author Yifang Dang Yifang Dang Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Validation Search for more papers by this author Mingtong Ma Mingtong Ma Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Validation Search for more papers by this author Fei Wang Fei Wang Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Validation Search for more papers by this author Junfang Xu Junfang Xu Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Methodology Search for more papers by this author Li Chen Li Chen Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Methodology Search for more papers by this author Tianhao Liu Tianhao Liu orcid.org/0000-0002-1991-5863 Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Visualization Search for more papers by this author Jianxia Chen Jianxia Chen Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Funding acquisition Search for more papers by this author Fan Zhang Fan Zhang Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Funding acquisition Search for more papers by this author Li Yang Li Yang Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Supervision Search for more papers by this author Qinghua Xu Qinghua Xu Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Supervision Search for more papers by this author Xuefei Hu Xuefei Hu Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Supervision Search for more papers by this author Heyong Wang Heyong Wang Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Supervision Search for more papers by this author Yiyan Fei Corresponding Author Yiyan Fei [email protected] orcid.org/0000-0002-2413-130X Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai, China Contribution: Software, Supervision Search for more papers by this author Chang Chen Corresponding Author Chang Chen [email protected] orcid.org/0000-0002-9981-3110 Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Conceptualization, Supervision Search for more papers by this author Haipeng Liu Corresponding Author Haipeng Liu [email protected] orcid.org/0000-0002-3338-6291 Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Institute of Nuclear Medicine, Tongji University School of Medicine, Shanghai, China Contribution: Conceptualization, Data curation, Formal analysis, Supervision, Funding acquisition, Writing - original draft, Project administration, Writing - review & editing Search for more papers by this author Jiani Gao Jiani Gao Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Validation, Writing - original draft, Writing - review & editing Search for more papers by this author Mengge Zheng Mengge Zheng Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Validation, Writing - original draft, Writing - review & editing Search for more papers by this author Xiangyang Wu Xiangyang Wu orcid.org/0000-0002-0444-7120 Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Validation, Writing - original draft, Writing - review & editing Search for more papers by this author Hang Zhang Hang Zhang orcid.org/0000-0001-9485-5883 Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai, China Contribution: Software Search for more papers by this author Hang Su Hang Su Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Software Search for more papers by this author Yifang Dang Yifang Dang Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Validation Search for more papers by this author Mingtong Ma Mingtong Ma Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Validation Search for more papers by this author Fei Wang Fei Wang Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Validation Search for more papers by this author Junfang Xu Junfang Xu Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Methodology Search for more papers by this author Li Chen Li Chen Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Methodology Search for more papers by this author Tianhao Liu Tianhao Liu orcid.org/0000-0002-1991-5863 Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Visualization Search for more papers by this author Jianxia Chen Jianxia Chen Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Funding acquisition Search for more papers by this author Fan Zhang Fan Zhang Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Funding acquisition Search for more papers by this author Li Yang Li Yang Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Supervision Search for more papers by this author Qinghua Xu Qinghua Xu Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Supervision Search for more papers by this author Xuefei Hu Xuefei Hu Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Supervision Search for more papers by this author Heyong Wang Heyong Wang Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Supervision Search for more papers by this author Yiyan Fei Corresponding Author Yiyan Fei [email protected] orcid.org/0000-0002-2413-130X Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai, China Contribution: Software, Supervision Search for more papers by this author Chang Chen Corresponding Author Chang Chen [email protected] orcid.org/0000-0002-9981-3110 Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Contribution: Conceptualization, Supervision Search for more papers by this author Haipeng Liu Corresponding Author Haipeng Liu [email protected] orcid.org/0000-0002-3338-6291 Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China Institute of Nuclear Medicine, Tongji University School of Medicine, Shanghai, China Contribution: Conceptualization, Data curation, Formal analysis, Supervision, Funding acquisition, Writing - original draft, Project administration, Writing - review & editing Search for more papers by this author Author Information Jiani Gao1,2,†, Mengge Zheng2,†, Xiangyang Wu2,†, Hang Zhang3, Hang Su1, Yifang Dang2,4, Mingtong Ma2, Fei Wang2, Junfang Xu2, Li Chen2, Tianhao Liu2, Jianxia Chen2,4, Fan Zhang2, Li Yang2, Qinghua Xu2, Xuefei Hu1, Heyong Wang5, Yiyan Fei *,3, Chang Chen *,1 and Haipeng Liu *,2,4,5,6 1Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China 2Clinical and Translational Research Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China 3Department of Optical Science and Engineering, Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Fudan University, Shanghai, China 4Shanghai Key Laboratory of Tuberculosis, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China 5Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China 6Institute of Nuclear Medicine, Tongji University School of Medicine, Shanghai, China † These authors contributed equally to this work. *Corresponding author. Tel: +86 21 31242571; E-mail: [email protected] *Corresponding author. Tel: +86 21 65115006 1008; E-mail: [email protected] *Corresponding author. Tel: +86 21 65115006 1116; E-mail: [email protected] EMBO Reports (2022)23:e53932https://doi.org/10.15252/embr.202153932 Full textView the full text of the articlePDFDownload PDF of article text and main figures. Peer ReviewDownload a summary of the editorial decision process including editorial decision letters, reviewer comments and author responses to feedback. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info Abstract Aberrant activation of stimulator of interferon genes (STING) is tightly associated with multiple types of disease, including cancer, infection, and autoimmune diseases. However, the development of STING modulators for the therapy of STING-related diseases is still an unmet clinical need. We employed a high-throughput screening approach based on the interaction of small-molecule chemical compounds with recombinant STING protein to identify functional STING modulators. Intriguingly, the cyclin-dependent protein kinase (CDK) inhibitor Palbociclib was found to directly bind STING and inhibit its activation in both mouse and human cells. Mechanistically, Palbociclib targets Y167 of STING to block its dimerization, its binding with cyclic dinucleotides, and its trafficking. Importantly, Palbociclib alleviates autoimmune disease features induced by dextran sulphate sodium or genetic ablation of three prime repair exonuclease 1 (Trex1) in mice in a STING-dependent manner. Our work identifies Palbociclib as a novel pharmacological inhibitor of STING that abrogates its homodimerization and provides a basis for the fast repurposing of this Food and Drug Administration-approved drug for the therapy of autoinflammatory diseases. SYNOPSIS Aberrant activation of STING is tightly associated with multiple types of diseases. Here, Palbociclib is identified as a pharmacological inhibitor of STING that can be repurposed for the therapy of STING-driven autoimmune diseases. High throughput screening of small molecule chemical compounds successfully identified STING modulators. Palbociclib directly targets STING tyrosine 167 and inhibits its activation by abrogating its dimerization. Palbociclib alleviates DSS-induced colitis and Trex1−/−-mediated tissue damage by reducing STING-mediated inflammation. Previous ArticleNext Article Read MoreAbout the coverClose modalView large imageVolume 23,Issue 6,07 June 2022This month's cover highlights the article PLETHORA‐WOX5 interaction and subnuclear localization control Arabidopsis root stem cell maintenance by Rebecca Corinna Burkart, Yvonne Stahl and colleagues. The image shows a maximum intensity projection of an Arabidopsis lateral root primordium expressing PLT3‐mVenus (yellow) under its native promoter counterstained with the membrane dye FM4‐64 (magenta). Yellow PLT3‐positive nuclear bodies are seen mainly in the central future columella stem cell (CSC).(Scientific image by Rebecca Corinna Burkart and Yvonne Stahl, Institute for Developmental Genetics, Heinrich‐Heine University, D̈sseldorf, Germany.) Volume 23Issue 67 June 2022In this issue RelatedDetailsLoading ..." @default.
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- W4223544904 title "CDK inhibitor Palbociclib targets STING to alleviate autoinflammation" @default.
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