MAPK/ERK通路
SH-SY5Y型
泛素连接酶
细胞生物学
干扰素
激酶
磷酸化
蛋白酶体
生物
泛素
化学
神经母细胞瘤
细胞培养
免疫学
生物化学
遗传学
基因
作者
D Chen,Cheng Chen,Jing‐Yu Tan,Jing Yang,Bangtao Chen
出处
期刊:Pathogens and Disease
[Oxford University Press]
日期:2023-01-01
卷期号:81
标识
DOI:10.1093/femspd/ftad011
摘要
Enterovirus 71 (EV71) can cause severe hand-foot-and-mouth disease with neurological complications. It has evolved multiple mechanisms to compromise the host type I interferon (IFN-I) response. In neuronal cells, EV71-mediated IFN-I antagonism may be associated with neural precursor cell-expressed developmentally downregulated 4-like (Nedd4L), the E3 ubiquitin ligase that can interact with alphaB-crystallin (CRYAB) in the regulation of Nav1.5 stability. Here, we investigated the effect of CRYAB stability on IFN-β promoter activity in neuronal SH-SY5Y cells infected with EV71, and its relations to Nedd4 L and extracellular signal-regulated kinases (ERK). Results showed that EV71 infection significantly caused CRYAB degradation via the Nedd4L-proteasome pathway, which required ERK-mediated phosphorylation of Serine 45 in CRYAB. Subsequently, it was observed that siRNA- or EV71-mediated CRYAB reduction limited Poly(dAT)-activated IFN-β promoter, and CRYAB stabilisation by U0126-mediated inhibition of ERK activation remarkably enhanced the activity of IFN-β promoter upon EV71 challenge. Collectively, we elucidate a novel mechanism by which ERK activation contributes to EV71 immune escape via CRYAB/IFN-β axis in SH-SY5Y cells, indicating that perturbing ERK activation is desirable for anti-EV71 therapy.
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