GRP78-binding protein regulates cAMP-induced glial fibrillary acidic protein expression in rat C6 glioblastoma cells
GRP78-binding protein regulates cAMP-induced glial fibrillary acidic protein expression in rat C6 glioblastoma cells
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DOI：
10.1016/j.febslet.2006.06.028
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发表时间：
2006-07-10
期刊：
影响因子：
3.5
通讯作者：
Kiuchi, Kazutoshi
中科院分区：
文献类型：
--
作者：
Oh-hashi, Kentaro;Hirata, Yoko;Kiuchi, Kazutoshi
我们先前报道了一种新的GRP78结合蛋白(GBP)主要在大鼠脑内表达，并且随着年龄的增长其表达逐渐下降。为了鉴定其生物学功能，我们建立了稳定高表达GBP的C6胶质母细胞瘤细胞。GBP的稳定过表达减弱了cAMP诱导的胶质纤维酸性蛋白(GFAP)基因的表达，并伴随着cAMP诱导的信号转导和转录激活因子3(STAT3)磷酸化的降低。其他明显的cAMP诱导的事件，包括细胞外信号调节的蛋白激酶磷酸化的一过性降低和细胞增殖的放缓，几乎不受GBP过表达的影响。最重要的是，针对内源性GBP的siRNA显著下调了C6胶质母细胞瘤细胞中GBP的表达，并显著增强了cAMP诱导的GFAP mRNA的表达，同时伴随着STAT3的过度磷酸化。这些结果提示了GBP通过STAT3磷酸化调控GFAP基因表达的新功能。(C)2006年欧洲生化学会联合会。爱思唯尔出版，版权所有。
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. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.