School of Pharmacology, The Fourth Military Medical University, Xi'an 710032, China.
School of Public Health, Xi'an Jiaotong University, Xi'an 710061, China.
Antiviral Res. 2015 Aug;120:7-15. doi: 10.1016/j.antiviral.2015.04.013. Epub 2015 May 1.
We previously reported that hepatitis B virus core protein (HBc) can bind to the Enhancer I (Enh I) domain and can accumulate with transcription coactivator cAMP response element (CRE). This raises the possibility that HBc may interact with CRE/CREB and regulate CRE transcription activation. In this study, we investigated the function and mechanisms of HBc in regulating CRE transcriptional activation using the HepG2 cell line. Our results showed the following: (1) HBc expression significantly increases HBV CRE transcriptional activation; (2) phosphorylation of the serine residues in the arginine-rich domain (ARD) of HBc protein impacts the function of transcriptional activation by the CRE; (3) HBc protein significantly increases HBV CRE transcriptional activation following forskolin treatment; (4) HBc nonspecifically binds to CRE and enhances the binding of the cAMP response element-binding protein (CREB) to CRE; and (5) HBc increases the concurrent accumulation of CREB and CBP at the CRE region. HBc activates Enh I through its binding to CRE, increasing the concurrent accumulation of CREB/CBP on CRE, and thus increases CRE transcriptional activation.
我们之前报道过乙型肝炎病毒核心蛋白 (HBc) 可以与增强子 I (Enh I) 结构域结合，并与转录共激活因子 cAMP 反应元件 (CRE) 积累。这就提出了这样一种可能性，即 HBc 可能与 CRE/CREB 相互作用并调节 CRE 转录激活。在这项研究中，我们使用 HepG2 细胞系研究了 HBc 在调节 CRE 转录激活中的功能和机制。我们的结果表明：(1) HBc 表达显著增加 HBV CRE 转录激活；(2) HBc 蛋白精氨酸丰富域 (ARD) 中丝氨酸残基的磷酸化影响 CRE 的转录激活功能；(3) 福司可林处理后 HBc 蛋白显著增加 HBV CRE 转录激活；(4) HBc 蛋白非特异性结合 CRE 并增强 cAMP 反应元件结合蛋白 (CREB) 与 CRE 的结合；(5) HBc 增加 CRE 区域 CREB 和 CBP 的同时积累。HBc 通过与 CRE 结合激活 Enh I，增加 CRE 上 CREB/CBP 的同时积累，从而增加 CRE 转录激活。
