title: CK2 induced RIG-I drives metabolic adaptations in IFNγ-treated glioma cells.
abstract: Given the known anti-tumorigenic properties of IFNγ, its effect on glioma cell survival was investigated. Though IFNγ had no effect on glioma cell viability, it induced cell cycle arrest. This was accompanied by increased expression of p53 and retinoic acid inducible gene (RIG-I). While RIG-I had no effect on glioma cell survival, it increased expression of p53 and its downstream target TP53 induced glycolysis and apoptosis regulator (TIGAR). IFNγ induced mitochondrial co-localization of RIG-I was concomitant with its ability to regulate ROS generation, oxidative phosphorylation (OXPHOS) and key enzymes involved in glycolysis and pentose phosphate pathway. Importantly, metabolic gene profiling indicated a suppressed glycolytic pathway in glioma cells upon IFNγ treatment. In addition, IFNγ mediated increase in casein kinase 2 (CK2) expression positively regulated RIG-I expression. These findings demonstrate how IFNγ induced CK2 regulates RIG-I to drive a complex program of metabolic adaptation and redox homeostasis, crucial for determining glioma cell fate.
authors.affiliation: National Brain Research Centre, Manesar 122 051, Haryana, India.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Ghildiyal
authors.affiliation: National Brain Research Centre, Manesar 122 051, Haryana, India. Electronic address: ellora@nbrc.ac.in.
authors.forename: Ellora
authors.initials: E
authors.lastname: Sen
mesh_terms: D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D000071457:DEAD Box Protein 58; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006019:Glycolysis / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011971:Receptors, Immunologic
chemical_list: C573415:IFNG protein, human; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic; D007371:Interferon-gamma; D047390:Casein Kinase II; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58
keywords: IFNγ; Metabolism; RIG-I; ROS