HBx protein of hepatitis B virus interacts with the C-terminal portion of a novel human proteasome alpha-subunit.

Two-hybrid protein interaction screening in yeast was used to identify proteins that interact with the HBx nonstructural protein of hepatitis B virus (HBV). A new human member of the proteasome alpha-subunit family was obtained. Its protein sequence closely resembles the 28 kD subunits from other organisms. The interaction with HBx was abolished by a two amino-acid insertion behind position 128 in HBx, in a region previously found to be essential for its transcriptional transactivation function. These data support a model of HBx acting indirectly on transcriptional processes. By binding to a specific proteasome alpha-subunit, HBx might interfere with degradative processes, thereby enhancing the half-life of different transcription factors and other nuclear regulatory proteins. Interaction with the Hu 28k proteasome subunit could thus provide a unifying explanation for the markedly pleiotropic effects of HBx.