title: Parafibromin Is a Component of IFN-γ-Triggered Signaling Pathways That Facilitates JAK1/2-Mediated Tyrosine Phosphorylation of STAT1.
abstract: IFN-γ (also known as type II IFN) is a cytokine that is critically involved in antiviral and immunomodulatory effects. IFN-γ activates JAK1 and JAK2, which lead to the phosphorylation and activation of the transcription factor STAT1. Whether and how additional molecules are involved in the process are not fully clear. In this study, we identified parafibromin as an important component of the IFN-γ-triggered signaling pathways. Overexpression of parafibromin promoted IFN-γ-triggered phosphorylation of STAT1 at Tyr(701), subsequent expression of downstream genes, and cellular antiviral response, whereas knockdown of parafibromin had opposite effects. Parafibromin interacted with JAK1/2, promoted the interactions of JAK1-JAK2 and JAK1/2-STAT1, and promoted tyrosine phosphorylation of STAT1 by JAKs after IFN-γ stimulation. Our results reveal a previously uncharacterized role of parafibromin in mediating IFN-γ-triggered signaling and cellular effects.
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan 430072, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wei
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan 430072, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Lian
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan 430072, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhong
authors.affiliation: College of Life Sciences, Medical Research Institute, Collaborative Innovation Center for Viral Immunology, Wuhan University, Wuhan 430072, China shuh@whu.edu.cn.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Shu
mesh_terms: D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000276:immunology; D057809:HEK293 Cells; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D053613:Janus Kinase 1 / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism*; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C454900:CDC73 protein, human; D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D025521:Tumor Suppressor Proteins; D007371:Interferon-gamma; C507904:JAK1 protein, human; C507924:JAK2 protein, human; D053613:Janus Kinase 1; D053614:Janus Kinase 2