p120-catenin promotes innate antiviral immunity through stabilizing TBK1-IRF3 complex. 2023

Haifeng Wu, and Xiuqing Yan, and Liang Zhao, and Xiang Li, and Ximing Li, and Yi Zhang, and Changping Gu, and Fan Yang, and Jingting Yan, and Yalin Lou, and Yufei Li, and Li Yang, and Xiaofeng Qin, and Yuelan Wang
Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766 Jingshi Road, Jinan 250014, Shandong, China; Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Shandong First Medical University, Shandong Institute of Anesthesia and Respiratory Critical Care Medicine, No. 16766 Jingshi Road, Jinan 250014, Shandong, China.

TBK1-IRF3 complex plays vital roles in antiviral immune responses, its regulatory mechanisms are currently incompletely understood. p120-catenin (p120), an armadillo-repeat protein, mainly regulates the stability of classical cadherins and the development of epithelial-to-mesenchymal transitions (EMTs). Here we report that p120 is a positive regulator of type I IFN production. Ectopic expression of p120 enhanced Vesicular stomatitis virus and Sendai-virus-induced type I IFN production, whereas knockdown of p120 expression suppressed type I IFN production. Mechanistically, p120 promoted phosphorylation of IRF3 via stabilizing the TBK1-IRF3 complex. Consistently, p120 knock down mice are more susceptible to VSV infection as indicated by higher tissue viral titers, less IFN-I production and greater infiltration of immune cells. This study reveals p120 as an important positive regulator in innate immunity and identifies that p120 facilitates host antiviral response through stabilizing TBK1-IRF3 complex.

UI MeSH Term Description Entries
D007113 Immunity, Innate The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS. Immunity, Native,Immunity, Natural,Immunity, Non-Specific,Resistance, Natural,Innate Immune Response,Innate Immunity,Immune Response, Innate,Immune Responses, Innate,Immunity, Non Specific,Innate Immune Responses,Native Immunity,Natural Immunity,Natural Resistance,Non-Specific Immunity
D007370 Interferon Type I Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA). Interferons Type I,Type I Interferon,Type I Interferons,Interferon, Type I,Interferons, Type I
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D000095002 Delta Catenin A CATENIN protein that plays a critical role in cell adhesion and tissue morphogenesis by regulating the surface stability of C-, E-, and N- CADHERINS. CTNND1 Protein,CTNND2 Protein,Cadherin-Associated Src Substrate p120,Catenin Delta-1,Catenin Delta-2,Catenin p120(ctn) Protein,Catenin p120ctn Protein,Catenin, Delta,Delta Catenins,Delta-Catenin,Neurojungin,p120(cas),p120(ctn),p120-catenin,p120cas,p120ctn,Catenins, Delta,Delta-1, Catenin,Protein, CTNND1,Protein, CTNND2,Protein, Catenin p120ctn
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D017346 Protein Serine-Threonine Kinases A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. Protein-Serine-Threonine Kinases,Serine-Threonine Protein Kinase,Serine-Threonine Protein Kinases,Protein-Serine Kinase,Protein-Serine-Threonine Kinase,Protein-Threonine Kinase,Serine Kinase,Serine-Threonine Kinase,Serine-Threonine Kinases,Threonine Kinase,Kinase, Protein-Serine,Kinase, Protein-Serine-Threonine,Kinase, Protein-Threonine,Kinase, Serine-Threonine,Kinases, Protein Serine-Threonine,Kinases, Protein-Serine-Threonine,Kinases, Serine-Threonine,Protein Kinase, Serine-Threonine,Protein Kinases, Serine-Threonine,Protein Serine Kinase,Protein Serine Threonine Kinase,Protein Serine Threonine Kinases,Protein Threonine Kinase,Serine Threonine Kinase,Serine Threonine Kinases,Serine Threonine Protein Kinase,Serine Threonine Protein Kinases
D050838 Interferon Regulatory Factor-3 An interferon regulatory factor that is expressed constitutively and undergoes POST-TRANSLATIONAL MODIFICATION following viral infection. PHOSPHORYLATION of IRF-3 causes the protein to be translocated from the CYTOPLASM to CELL NUCLEUS where it binds DNA, and activates transcription. IRF-3 Transcription Factor,IFN-Regulatory Factor 3,IFN Regulatory Factor 3,IRF 3 Transcription Factor,Interferon Regulatory Factor 3,Transcription Factor, IRF-3
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

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