The PreS2 Activators of the Hepatitis B Virus: Activators of Tumour Promoter Pathways

  • E. Hildt
  • P. H. Hofschneider
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 154)


In addition to causing acute and chronic hepatitis, hepatitis B virus (HBV) is considered to be a major cliological factor in the development of human hepatocellular carcinoma (HCC). Epidemiological studies have demonstrated an approximately 10-fold increase in the relative risk of HCC among HBV carried compared to noncarriers. Almost all HBV-associated HCCs studied so far harbor chromosomally integrated HBV DNA. Integrated viral DNA can encode two types of transcriptional activators, the HBx protein and the PreS2 activators [the large surface proteins (LHBs) and truncated middle surface proteins (MHBs)]. The activator function of the PreS2 activators is based on the cytoplasmic orientation of the PreS2 domain. The PreS2 domain is PKC-dependent phosphorylated. Moreover, the PreS2 domain binds of PKCa/β and triggers a PKC-dependent activation of the c-Raf-1/MAP2-kinase signal transduction cascade, resulting in an activation of transcription factors such as AP-1 and NF-kB. Furthermore, by activation of this signaling cascade, the PreS2 activators cause an increased proliferation rate of hepatocytes. According to the two-step model of carcinogenesis (initiation/promotion), the PreS2 activators could exert a tumour-promoter-like function by activation of the PKC/c-Raf-1/MAP2-kinase signaling cascade: cells harboring critical mutations (initiation) may be positively selected (promotion). Such a multistep process may account for the long latency period in HCC development, but it also leads to the hypothesis that each tumor reflects an individual case.


Increase Proliferation Rate Transcriptional Activator Function PreS2 Activator PreS2 Domain Virus Transgenic Mouse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag Berlin · Heidelberg 1998

Authors and Affiliations

  • E. Hildt
    • 1
  • P. H. Hofschneider
    • 2
  1. 1.Institute of Experimental SurgeryTechnical University of MunichMunichGermany
  2. 2.Max Planck Institute of BiochemistryDepartment of Viral ResearchMartinsriedGermany

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