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Hepatitis C virus core protein enhances the activation of the transcription factor, Elk1, in response to mitogenic stimuli
Author(s) -
Fukuda Katsuhiko,
Tsuchihara Katsuya,
Hijikata Makoto,
Nishiguchi Shuhei,
Kuroki Tetsuo,
Shimotohno Kunitada
Publication year - 2001
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2001.20794
Subject(s) - mapk/erk pathway , protein kinase a , microbiology and biotechnology , kinase , signal transduction , phosphorylation , biology , mitogen activated protein kinase kinase , duck hepatitis b virus , transcription factor , mitogen activated protein kinase , chemistry , virology , hepatitis b virus , virus , biochemistry , hepadnaviridae , gene
Mitogen‐activated protein kinase (MAPK) pathways play key roles in cell proliferation, transformation of mammalian cells, and the stress response. We and other investigators showed that hepatitis C virus (HCV) core protein has an oncogenic potential, but its mechanism has remained unknown. We previously demonstrated that the MAPK‐extra‐cellular signal—regulated kinase (ERK) kinase (MEK)‐ERK pathway and its downstream target, the serum response element (SRE), is activated in BALB/3T3 cells producing HCV core protein. To elucidate the precise mechanism by which HCV core protein activates the MEK‐ERK pathway, we transiently expressed HCV core protein in several cell lines and studied the signal transduction of the pathway, using Gal4‐Elk1 luciferase assay, in vitro kinas assay of MAPK, and Western blotting analysis. We discovered that, in the presence of mitogenic signal, HCV core protein enhanced Elk1 activation working downstream of MEK without affecting ERK activity 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 hepatocarcinogenesis.