The hepatitis B virus (HBV) core protein enhances the transcription activation of CRE via the CRE/CREB/CBP pathway.
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.
School of Pharmacology, The Fourth Military Medical University, Xi'an 710032, China.
An
A
Xiang
School of Public Health, Xi'an Jiaotong University, Xi'an 710061, China.
Fengling
F
Ren
School of Pharmacology, The Fourth Military Medical University, Xi'an 710032, China.
Xiaoying
X
Lei
School of Pharmacology, The Fourth Military Medical University, Xi'an 710032, China.
Ju
J
Zhang
School of Pharmacology, The Fourth Military Medical University, Xi'an 710032, China.
Ruijuan
R
Guo
School of Pharmacology, The Fourth Military Medical University, Xi'an 710032, China.
Zifan
Z
Lu
School of Pharmacology, The Fourth Military Medical University, Xi'an 710032, China.
Yanhai
Y
Guo
D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D056945:Hep G2 Cells; D006512:Hepatitis B Core Antigens / Q000378:metabolism*; D006515:Hepatitis B virus / Q000502:physiology*; D022781:Hepatocytes / Q000821:virology; D054884:Host-Pathogen Interactions; D006801:Humans; D015533:Transcriptional Activation; D014758:Viral Core Proteins / Q000378:metabolism*
D017362:Cyclic AMP Response Element-Binding Protein; D006512:Hepatitis B Core Antigens; D014758:Viral Core Proteins; C534392:p22 core protein, hepatitis B virus
HBV core protein; Phosphorylation; Transcriptional regulation; cAMP response element