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 hepatiti s B virus (HBV). A new human member of the proteasome alpha-subunit fa mily was obtained. Its protein sequence closely resembles the 28 kD su bunits from other organisms. The interaction with HBx was abolished by a two amino-acid insertion behind position 128 in HBx, in a region pr eviously found to be essential for its transcriptional transactivation function. These data support a model of HBx acting indirectly on tran scriptional processes. By binding to a specific proteasome alpha-subun it, HBx might interfere with degradative processes, thereby enhancing the half-life of different transcription factors and other nuclear reg ulatory proteins. Interaction with the Hu 28k proteasome subunit could thus provide a unifying explanation for the markedly pleiotropic effe cts of HBx.