title: Inhibition of casein kinase 2 modulates XBP1-GRP78 arm of unfolded protein responses in cultured glial cells.
abstract: Stress signals cause abnormal proteins to accumulate in the endoplasmic reticulum (ER). Such stress is known as ER stress, which has been suggested to be involved in neurodegenerative diseases, diabetes, obesity and cancer. ER stress activates the unfolded protein response (UPR) to reduce levels of abnormal proteins by inducing the production of chaperon proteins such as GRP78, and to attenuate translation through the phosphorylation of eIF2α. However, excessive stress leads to apoptosis by generating transcription factors such as CHOP. Casein kinase 2 (CK2) is a serine/threonine kinase involved in regulating neoplasia, cell survival and viral infections. In the present study, we investigated a possible linkage between CK2 and ER stress using mouse primary cultured glial cells. 4,5,6,7-tetrabromobenzotriazole (TBB), a CK2-specific inhibitor, attenuated ER stress-induced XBP-1 splicing and subsequent induction of GRP78 expression, but was ineffective against ER stress-induced eIF2α phosphorylation and CHOP expression. Similar results were obtained when endogenous CK2 expression was knocked-down by siRNA. Immunohistochemical analysis suggested that CK2 was present at the ER. These results indicate CK2 to be linked with UPR and to resist ER stress by activating the XBP-1-GRP78 arm of UPR.
authors: Department of Pharmacotherapy, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Hiroshima, Japan. toruh@hiroshima-u.ac.jp
authors: Toru
authors: T
authors: Hosoi
authors: Kenta
authors: K
authors: Korematsu
authors: Naohiro
authors: N
authors: Horie
authors: Takahiro
authors: T
authors: Suezawa
authors: Yasunobu
authors: Y
authors: Okuma
authors: Yasuyuki
authors: Y
authors: Nomura
authors: Koichiro
authors: K
authors: Ozawa
mesh_terms: D051702:Activating Transcription Factor 6 / Q000378:metabolism; D000818:Animals; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006360:Heat-Shock Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D012326:RNA Splicing / Q000187:drug effects / Q000235:genetics; D000071701:Regulatory Factor X Transcription Factors; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology; D056811:Unfolded Protein Response / Q000187:drug effects; D000071717:X-Box Binding Protein 1
chemical_list: C405354:4,5,6,7-tetrabromobenzotriazole; D051702:Activating Transcription Factor 6; C497112:Atf6 protein, mouse; D004268:DNA-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D047428:Protein Kinase Inhibitors; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D014230:Triazoles; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D051742:Transcription Factor CHOP; D047390:Casein Kinase II