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 process is not understood. In cell culture, HBx exhibits pleiotropic activities affecting transcription, DNA repair, cell growth, and apoptotic cell death. Numerous cellular proteins including the p127-kDa subunit of UV-damaged DNA-binding activity have been reported to interact with HBx but the functional significance of these interactions remains unclear. Here we show that the binding of HBx to p127 interferes with cell viability. Mutational analysis reveals that HBx contacts p127 via a region to which no function has been assigned previously. An HBx variant bearing a single-charge reversal substitution within this region loses p127 binding and concomitant cytotoxicity. This mutant regains activity when directly fused to p127. These studies confirm that p127 is an important cellular target of HBx, and they indicate that HBx does not exert its effect by sequestering p127, and thereby preventing its normal function, but instead by conferring to p127 a deleterious activity.
Lin-Marq
N
N
Department of Genetics and Microbiology, University Medical Centre, Rue Michel-Servet 1, Geneva 4, 1211, Switzerland.
Bontron
S
S
Leupin
O
O
Strubin
M
M
D000595:Amino Acid Sequence; D016923:Cell Death; D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000821:virology; D008969:Molecular Sequence Data; D008970:Molecular Weight; D016296:Mutagenesis; D012441:Saccharomyces cerevisiae / Q000378:metabolism / Q000528:radiation effects; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D014162:Transfection; D014466:Ultraviolet Rays; D054334:Viral Regulatory and Accessory Proteins
D004268:DNA-Binding Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein