Preferred Label : HBx Signaling Pathway;
NCIt related terms : Calcium Signaling by HBx of Hepatitis B virus;
Alternative definition : BIOCARTA: Hepatitis B is a small DNA virus that contains only 4 open reading frames
in its genome. Three of these ORFs have been identified as the envelope, capsid and
polymerase genes, while the function of the fourth has remained unknown until recently.
The fourth reading frame has been called the X gene and produces HBx protein that
is essential for viral replication in liver cells and acts broadly to activate a variety
of transcription factors. One hypothesis of HBx activity has been that it enters the
nucleus to act as a transcriptional regulator. One piece of evidence supporting this
mechanism of HBx action is that HBx interacts with the transcription factor CREB and
increases its DNA-binding activity. This mechanism does not explain all of the effects
of HBx however. Another hypothesis for the HBx mechanism of action is that HBx increases
calcium release into the cytoplasm. This mechanism of action is consistent with the
variety of transcription factors and kinases affected by HBx since calcium signaling
affects many different signaling pathways. HBx does not appear to interact directly
with Ras or protein kinases but does appear to activate the calcium activate protein
kinase Pyk2. A dominant negative form of Pyk2 blocks HBx activity and the involvement
of calcium in HBx activation of Pyk2 is indicated by the action of several molecular
probes that alter cytosolic calcium signaling. BAPTA-AM chelates cytosolic and blocks
HBx action. Cyclosporin A blocks mitochondrial calcium signaling and also blocked
HBx signaling. CGP37157 is a compound that blocks the mitochondrial sodium calcium
pump and also blocks hepatitis B viral replication, indicating that mitochondrial
calcium signaling is the target of HBx function. Compounds that elevate cytoplasmic
calcium levels (valinomycin and thapsigargin) increase the rate of replication of
viruses that lack HBx, further supporting the role of HBx as an inducer of intracellular
calcium signaling. The mechanism by which HBx causes calcium release is not yet known.
Src activation appears to induce viral replication while Ras signaling does not, suggesting
that the activation of Ras signaling by HBx may play a distinct function, perhaps
the induction of cancer. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_HBxPathway;
Origin ID : C39100;
UMLS CUI : C1512294;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
