Hepatitis B virus X protein is both a substrate and a potential inhibitor of the proteasome complex

Citation
Zy. Hu et al., Hepatitis B virus X protein is both a substrate and a potential inhibitor of the proteasome complex, J VIROLOGY, 73(9), 1999, pp. 7231-7240
Citations number
57
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Microbiology
Journal title
JOURNAL OF VIROLOGY
ISSN journal
0022-538X → ACNP
Volume
73
Issue
9
Year of publication
1999
Pages
7231 - 7240
Database
ISI
SICI code
0022-538X(199909)73:9<7231:HBVXPI>2.0.ZU;2-N
Abstract
The hepatitis B virus X protein (HBX) is essential for the establishment of HBV infection in vivo and exerts a pleiotropic effect on diverse cellular functions. The yeast two-hybrid system had indicated that HBX could interac t with two subunits of the 26S proteasome. Here we demonstrate an associati on in vivo of HBX with the 26S proteasome complex by coimmunoprecipitation and colocalization upon sucrose gradient centrifugation. Expression of HBX in HepG2 cells caused a modest decrease in the proteasome's chymotrypsin- a nd trypsin-like activities and in hydrolysis of ubiquitinated lysozyme, sug gesting that HBX functions as an inhibitor of proteasome. In these cells, H BX is degraded with a half-life of 30 min. Proteasome inhibitors retarded t his rapid degradation and caused a marked increase in the level of HBX and an accumulation of HBX in polyubiquitinated form. Thus, the low intracellul ar level of HBX in due to rapid proteolysis by the ubiquitin-proteasome pat hway. Surprisingly, the proteasome inhibitors blocked the transactivation b y HBX, and this effect was not a result of a squelching phenomenon due to H BX accumulation. Therefore, proteasome function is possibly required for th e transactivation function of HBX. The inhibition of protein breakdown by p roteasomes may account for the multiple actions of HBX and may be an import ant feature of HBV infection, possibly in helping stabilize viral gene prod ucts and suppressing antigen presentation.