Notably, preS/S sequences deleted at the 3’-end that produce functionally active C-terminally truncated middle surface protein (MHBSt) have been found in many HBV DNA positive HCC patients, and protein kinase C (PKC)-dependent activation of the c-Raf-1/MEK/Erk2 signaling pathway was triggered by MHBSt retained in the endoplasmic reticulum (ER) in MHBSt transgenic mice and hepatoma cells, which, leading to regulation of AP-1 and enhanced proliferative activity of hepatocytes [5]. The gene discussed is MAPK1; the disease is hepatocellular carcinoma.