Hepatitis B virus X protein interferes with cell viability through interaction with the p127-kDa UV-damaged DNA-binding protein

The hepatitis B virus X protein (HBx) is essential for establishing natural viral Infection and has been Implicated in the development of liver cancer associated with chronic infection. The basis for HBx function in either pr ocess is not understood. In cell culture, HBx exhibits pleiotropic activiti es affecting transcription, DNA repair, cell growth, and apoptotic cell dea th. Numerous cellular proteins including the p127-kDa subunit of UV-damaged DNA-binding activity have been reported to interact with HBx but the funct ional significance of these interactions remains unclear. Here we show that the binding of HBx to p127 interferes with cell viability. Mutational anal ysis reveals that HBx contacts p127 via a region to which no function has b een assigned previously. An HBx variant bearing a single-charge reversal su bstitution within this region loses p127 binding and concomitant cytotoxici ty. This mutant regains activity when directly fused to p127. These studies confirm that p127 is an important cellular target of HBx, and they indicat e that HBx does not exert its effect by sequestering p127, and thereby prev enting its normal function, but instead by conferring to p127 a deleterious activity, (C) 2001 Academic Press.