title: An internal segment (residues 58-119) of the hepatitis B virus X protein is sufficient to activate MAP kinase pathways in mouse liver.
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.
authors.affiliation: Department of Biochemistry, University of Delhi South Campus, Benito Juarez, New Delhi, India.
authors.forename: R
authors.initials: R
authors.lastname: Nijhara
authors.forename: S S
authors.initials: SS
authors.lastname: Jana
authors.forename: S K
authors.initials: SK
authors.lastname: Goswami
authors.forename: V
authors.initials: V
authors.lastname: Kumar
authors.forename: D P
authors.initials: DP
authors.lastname: Sarkar
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D004789:Enzyme Activation; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D020935:MAP Kinase Signaling System; D051379:Mice; D009154:Mutation; D010766:Phosphorylation; D015398:Signal Transduction; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D017931:DNA Primers; D015534:Trans-Activators; D018808:Transcription Factor AP-1; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein