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 regulatory functions in cellular transcription and virus-induced transformation 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 regulates cell proliferation. Loss of LZIP function in NIH 3T3 cells triggers morphological 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 that LZIP might serve a novel cellular tumor suppressor function that is targeted by the HCV core.
Jin
D Y
DY
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA. dyjin@hkucc.hku.hk
Wang
H L
HL
Zhou
Y
Y
Chun
A C
AC
Kibler
K V
KV
Hou
Y D
YD
Kung
H
H
Jeang
K T
KT
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D002460:Cell Line; D002472:Cell Transformation, Viral; D017362:Cyclic AMP Response Element-Binding Protein; D003593:Cytoplasm / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D019281:Dimerization; D051790:G-Box Binding Factors; D006367:HeLa Cells; D016174:Hepacivirus / Q000472:pathogenicity*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014758:Viral Core Proteins / Q000502:physiology*
D050976:Basic-Leucine Zipper Transcription Factors; C107941:CREB3 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D004268:DNA-Binding Proteins; D051790:G-Box Binding Factors; D014157:Transcription Factors; D014758:Viral Core Proteins