Hepatitis C virus core protein-induced loss of LZIP function correlates with cellular transformation

Hepatitis C virus (HCV) is the major etiological agent of blood-borne non-A non-B hepatitis and a leading cause of liver cirrhosis and hepatocellular carcinoma worldwide. HCV core protein is a multifunctional protein with reg ulatory functions in cellular transcription and virus-induced transformatio n and pathogenesis. Here we report on the identification of a bZIP nuclear transcription protein as an HCV core cofactor for transformation. This bZIP factor, designated LZIP, activates CRE-dependent transcription and regulat es cell proliferation. Loss of LZIP function in NIH 3T3 cells triggers morp hological transformation and anchorage-independent growth. We show that HCV core protein aberrantly sequesters LZIP in the cytoplasm, inactivates LZIP function and potentiates cellular transformation. Our findings suggest tha t LZIP might serve a novel cellular tumor suppressor function that is targe ted by the HCV core.