HBx公司
安普克
PI3K/AKT/mTOR通路
蛋白激酶B
cccDNA
细胞生物学
化学
磷酸化
信号转导
蛋白激酶A
癌症研究
乙型肝炎病毒
生物
病毒学
病毒
乙型肝炎表面抗原
作者
Jumi Kim,Hyeonjoong Kwon,Fadia Kalsoom,Muhammad Azhar Sajjad,Hyun Woong Lee,Jin Hong Lim,Jaesung Jung,Yong‐Joon Chwae,Sun Park,Ho‐Joon Shin,Kyongmin Kim
出处
期刊:Microorganisms
[MDPI AG]
日期:2022-02-23
卷期号:10 (3): 498-498
被引量:4
标识
DOI:10.3390/microorganisms10030498
摘要
Ca2+/calmodulin-dependent protein kinase II (CaMKII), which is involved in the calcium signaling pathway, is an important regulator of cancer cell proliferation, motility, growth, and metastasis. The effects of CaMKII on hepatitis B virus (HBV) replication have never been evaluated. Here, we found that phosphorylated, active CaMKII is reduced during HBV replication. Similar to other members of the AMPK/AKT/mTOR signaling pathway associated with HBV replication, CaMKII, which is associated with this pathway, was found to be a novel regulator of HBV replication. Overexpression of CaMKII reduced the expression of covalently closed circular DNA (cccDNA), HBV RNAs, and replicative intermediate (RI) DNAs while activating AMPK and inhibiting the AKT/mTOR signaling pathway. Findings in HBx-deficient mutant-transfected HepG2 cells showed that the CaMKII-mediated AMPK/AKT/mTOR signaling pathway was independent of HBx. Moreover, AMPK overexpression reduced HBV cccDNA, RNAs, and RI DNAs through CaMKII activation. Although AMPK acts downstream of CaMKII, AMPK overexpression altered CaMKII phosphorylation, suggesting that CaMKII and AMPK form a positive feedback loop. These results demonstrate that HBV replication suppresses CaMKII activity, and that CaMKII upregulation suppresses HBV replication from cccDNA via AMPK and the AKT/mTOR signaling pathway. Thus, activation or overexpression of CaMKII may be a new therapeutic target against HBV infection.
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