Activation of p53 tumor suppressor by hepatitis C virus core protein

In addition to being a structural protein that packages the viral genomic R NA, hepatitis C virus (HCV) core protein possesses regulatory functions. In this report, we demonstrate that the HCV core protein could enhance the ge ne transactivation activity of the tumor suppressor p53, regardless of whet her p53 was derived from an exogenous or an endogenous gene. The activation of p53 by the HCV core protein was supported by the observation that the H CV core protein could enhance the expression of p21(waf1/Cip1), a downstrea m effector gene of p53, in a p53-dependent manner. Further studies indicate d that the HCV core protein could also suppress hepatocellular growth via p 53. The HCV core protein and p53 could bind to each other in vitro, which w as evidenced by the coimmunoprecipitation, the GST pull-down, and the Far-W estern blot assays. The deletion-mapping analysis indicated that the carbox y-terminal sequence of p53 located between amino acids 366 and 380 was requ ired for the core protein binding. These results raised the possibility tha t the HCV core protein might activate p53 through direct physical interacti on. The persistent perturbation of p53 activity by the HCV core protein dur ing chronic infection may have important consequences in HCV pathogenesis. (C) 1999 Academic Press.