GRP78-binding protein regulates cAMP-induced glial fibrillary acidic protein expression in rat C6 glioblastoma cells.
We previously reported that a novel GRP78-binding protein (GBP) is predominantly expressed in rat brain and its expression declines through the aging process. To characterize its biological function, we established C6 glioblastoma cells that stably overexpressed GBP. Stable overexpression of GBP attenuated cAMP-induced expression of the glial fibrillary acidic protein (GFAP) gene, which was accompanied by a decrease in cAMP-induced signal transducer and activators of transcription 3 (STAT3) phosphorylation. Other distinct cAMP-induced events, including a transient reduction in extracellular signal-regulated protein kinase phosphorylation and a slowdown in cell proliferation, were hardly affected by GBP overexpression. Most importantly, treatment with siRNA against endogenous GBP markedly downregulated GBP expression in C6 glioblastoma cells, and dramatically augmented cAMP-induced GFAP mRNA expression in parallel with hyper-phosphorylation of STAT3. These results suggest a novel function of GBP in regulating GFAP gene expression via STAT3 phosphorylation.
Oh-hashi
Kentaro
K
Department of Biomolecular Science, Faculty of Engineering, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Hirata
Yoko
Y
Koga
Hisashi
H
Kiuchi
Kazutoshi
K
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism*; D005909:Glioblastoma / Q000473:pathology*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000091342:Endoplasmic Reticulum Chaperone BiP
D002352:Carrier Proteins; D005576:Colforsin; D000242:Cyclic AMP; D005904:Glial Fibrillary Acidic Protein; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP; C512354:Tmem132a protein, rat