Hepatitis C virus core protein enhances the activation of the transcription factor, Elk1, in response to mitogenic stimuli

Mitogen-activated protein kinase (MAPK) pathways play key roles in cell pro liferation, transformation of mammalian cells, and the stress response. We and other investigators showed that hepatitis C virus (HCV) core protein ha s an oncogenic potential, but its mechanism has remained unknown. We previo usly demonstrated that the MAPK-extracellular signal-regulated kinase (ERK) kinase (MEK)-ERK pathway and its downstream target, the serum response ele ment (SRE), is activated in BALB/3T3 cells producing HCV core protein. To e lucidate the precise mechanism by which HCV core protein activates the MEK- ERK pathway, we transiently expressed HCV core protein in several cell line s and studied the signal transduction of the pathway, using Gal4-Elk1 lucif erase assay, in vitro kinase assay of MAPK, and Western blotting analysis. We discovered that, in the presence of mitogenic signal, HCV core protein e nhanced Elk1 activation working downstream of MEK without affecting ERK act ivity and Elk1 phosphorylation. Our data suggest that HCV core protein may activate Elk1 through a pathway alternative to the typical phosphorylation cascade. These findings might give new insights into the role of HCV in hep atocarcinogenesis.