An internal segment (residues 58-119) of the hepatitis B virus X protein is sufficient to activate MAP kinase pathways in mouse liver

FEBS Lett. 2001 Aug 24;504(1-2):59-64. doi: 10.1016/s0014-5793(01)02773-9.

Abstract

The human hepatitis B virus X protein (HBx) is known as a dual-specificity transactivator stimulating the transcriptional machinery in the nucleus and signal transduction pathways in the cytoplasm. HBx-induced activation of mitogen-activated protein kinase (MAPK) signaling cascades is considered to play an important role in hepatitis B virus-mediated hepatocarcinogenesis. Herein, we have identified the regions of HBx that are crucial for activating such signaling cascades in vivo. A truncated mutant incorporating regions C-E (amino acids 58-140) was as effective as the full-length HBx in activating MAPKs and enhancing activator protein-1 binding activity. While deletion of region C (amino acids 58-84) or D (amino acids 85-119) led to a drastic loss of function, region E (amino acids 120-140) was dispensable for the activation of signaling cascades. Overall, these findings provide the first evidence for the requirement of domain 58-119 of HBx in transmitting mitogenic signals to the nucleus in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Western
  • DNA Primers
  • Enzyme Activation
  • Liver / cytology
  • Liver / enzymology*
  • MAP Kinase Signaling System*
  • Mice
  • Mutation
  • Phosphorylation
  • Signal Transduction
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transcription Factor AP-1 / metabolism
  • Viral Regulatory and Accessory Proteins

Substances

  • DNA Primers
  • Trans-Activators
  • Transcription Factor AP-1
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein