Transactivation of human hepatitis B virus X protein, HBx, operates through a mechanism distinct from protein kinase C and okadaic acid activation pathways.
Human hepatitis B virus (HBV) X protein, HBx, transactivates virus and host genes through a wide variety of cis-elements. Expression of HBx is controlled by HBV enhancer 1 (Enh1). Both Enh1 and the core sequence of Enh1, which consists of an AP-1 related site (cFAP1) and a C stretch, respond to HBx and a phorbol ester (TPA). Biochemical pathways of the responses to HBx and TPA are still controversial. We therefore asked whether HBx and TPA stimulate Enh1 core activity through a common process. Protein kinase C (PKC) inhibitors, H-7 and staurosporin, did not inhibit HBx transactivation at concentrations sufficient to abolish the TPA effects in HepG2 cells. Although HBx transactivation synergized independently with TPA or a phosphoprotein phosphatase inhibitor, okadaic acid (OA), the PKC inhibitors eliminated only the TPA contribution. HBx transactivation required both the cFAP1 and the C stretch of the Enh1 core region; however, mutations in either or both of the two cis-elements demonstrated that TPA augmentation required only cFAP1. These results imply that HBx transactivation operates through a mechanism distinct from the PKC and OA activation pathways.
Murakami
S
S
Department of Biophysics, Medical School, Kanazawa University, Japan.
Cheong
J
J
Ohno
S
S
Matsushima
K
K
Kaneko
S
S
D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral; D004988:Ethers, Cyclic / Q000378:metabolism*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D019319:Okadaic Acid; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics*; D015533:Transcriptional Activation; D054334:Viral Regulatory and Accessory Proteins
D004279:DNA, Viral; D004988:Ethers, Cyclic; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D019319:Okadaic Acid; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate