title: Inhibition of Proteasome Activity Induces Aggregation of IFIT2 in the Centrosome and Enhances IFIT2-Induced Cell Apoptosis.
abstract: IFN-induced protein with tetratricopeptide repeats 2 (IFIT2), one of the most highly responsive interferon-stimulated genes, inhibits the proliferation and migration of cancer cells and regulates viral replication. IFIT2 has been demonstrated to be a cytoskeleton-associated protein that becomes enriched in the mitotic spindle of cells. However, the molecular mechanisms by which IFIT2 executes biological functions are largely unclear. The findings of this study showed that inhibiting the activation of proteasome led to the enrichment of IFIT2 and induced the aggregation of IFIT2 protein in the centrosome. Microtubule inhibitor colchicine and dynein inhibitor ciliobrevin inhibited the proteasome inhibitor-induced aggregation of IFIT2 protein in the centrosome. Intriguingly, IFIT2 and proteasome inhibitor worked together to induce the apoptosis of cancer cells. The results of the present study revealed that the inhibition of proteasome activity blocked the degradation of IFIT2 and promoted the aggregation of IFIT2 in the centrosome, which in turn induced cell apoptosis. In short, IFIT2 may be a potential target for cancer therapeutics.
authors.affiliation: Department of Clinical laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China;; Center for Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Clinical laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory Technology, Jiangxi Medical College, Shangrao, Jiangxi 334000, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Clinical laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Yunyuan
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Department of Clinical laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Lagen
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Clinical laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Yonglu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Clinical laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Zhanglin
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D051017:Apoptosis Regulatory Proteins; D018385:Centrosome / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D045325:HCT116 Cells; D057809:HEK293 Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008870:Microtubules / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins; D014404:Tubulin / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C484289:IFIT2 protein, human; D011506:Proteins; D016601:RNA-Binding Proteins; D014404:Tubulin; D046988:Proteasome Endopeptidase Complex; D004398:Dyneins
keywords: Aggregation; IFIT2; apoptosis; centrosome; proteasome