title: Casein Kinase 2 Is Linked to Stress Granule Dynamics through Phosphorylation of the Stress Granule Nucleating Protein G3BP1.
abstract: Stress granules (SGs) are large macromolecular aggregates that contain translation initiation complexes and mRNAs. Stress granule formation coincides with translational repression, and stress granules actively signal to mediate cell fate decisions by signaling to the translation apparatus to (i) maintain translational repression, (ii) mount various transcriptional responses, including innate immunity, and (iii) repress apoptosis. Previous work showed that G3BP1 is phosphorylated at serine 149, which regulates G3BP1 oligomerization, stress granule assembly, and RNase activity intrinsic to G3BP1. However, the kinase that phosphorylates G3BP1 was not identified, leaving a key step in stress granule regulation uncharacterized. Here, using chemical inhibition, genetic depletion, and overexpression experiments, we show that casein kinase 2 (CK2) promotes stress granule dynamics. These results link CK2 activity with SG disassembly. We also show that casein kinase 2 phosphorylates G3BP1 at serine 149 in vitro and in cells. These data support a role for casein kinase 2 in regulation of protein synthesis by downregulating stress granule formation through G3BP1.
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Lucas C
authors.initials: LC
authors.lastname: Reineke
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Antrix
authors.initials: A
authors.lastname: Jain
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.|Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Jason T
authors.initials: JT
authors.lastname: Kaelber
authors.affiliation: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Sung Yun
authors.initials: SY
authors.lastname: Jung
authors.affiliation: Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA rlloyd@bcm.edu.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Lloyd
mesh_terms: D018053:Arsenites / Q000633:toxicity; D002352:Carrier Proteins / Q000378:metabolism*; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000378:metabolism*; D004265:DNA Helicases; D005799:Genes, Dominant; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D000075223:Poly-ADP-Ribose Binding Proteins; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021122:Protein Subunits / Q000378:metabolism; D020365:RNA Helicases; D000067776:RNA Recognition Motif Proteins; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D018053:Arsenites; D002352:Carrier Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D047428:Protein Kinase Inhibitors; D021122:Protein Subunits; D000067776:RNA Recognition Motif Proteins; D047390:Casein Kinase II; D004265:DNA Helicases; C116070:G3BP1 protein, human; D020365:RNA Helicases; C015001:arsenite
keywords: G3BP1; casein kinase 2; stress granule