Artículo de revista
The viral transactivator HBx protein exhibits a high potential for regulation via phosphorylation through an evolutionarily conserved mechanism
Fecha
2012Registro en:
Infectious Agents and Cancer 2012, 7:27
Autor
Hernández, Sergio
Venegas Santos, Mauricio
Brahm Barril, Javier
Villanueva Arancibia, Rodrigo
Institución
Resumen
Background: Hepatitis B virus (HBV) encodes an oncogenic factor, HBx, which is a multifunctional protein that can
induce dysfunctional regulation of signaling pathways, transcription, and cell cycle progression, among other
processes, through interactions with target host factors. The subcellular localization of HBx is both cytoplasmic and
nuclear. This dynamic distribution of HBx could be essential to the multiple roles of the protein at different stages
during HBV infection. Transactivational functions of HBx may be exerted both in the nucleus, via interaction with
host DNA-binding proteins, and in the cytoplasm, via signaling pathways. Although there have been many studies
describing different pathways altered by HBx, and its innumerable binding partners, the molecular mechanism that
regulates its different roles has been difficult to elucidate.
Methods: In the current study, we took a bioinformatics approach to investigate whether the viral protein HBx
might be regulated via phosphorylation by an evolutionarily conserved mechanism.
Results: We found that the phylogenetically conserved residues Ser25 and Ser41 (both within the negative
regulatory domain), and Thr81 (in the transactivation domain) are predicted to be phosphorylated. By molecular 3D
modeling of HBx, we further show these residues are all predicted to be exposed on the surface of the protein,
making them easily accesible to these types of modifications. Furthermore, we have also identified Yin Yang sites
that might have the potential to be phosphorylated and O-β-GlcNAc interplay at the same residues.
Conclusions: Thus, we propose that the different roles of HBx displayed in different subcellular locations might be
regulated by an evolutionarily conserved mechanism of posttranslational modification, via phosphorylation.