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PMID: 10675342 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 19 ·No. 4 ·2000-02-15 ·Pages 729-40

Jin DY, Wang HL, Zhou Y, Chun AC, Kibler KV, Hou YD, Kung H, Jeang KT

Abstract

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.

MeSH Terms
3T3 Cells Amino Acid Sequence Animals Base Sequence Basic-Leucine Zipper Transcription Factors Cell Line Cell Transformation, Viral Cyclic AMP Response Element-Binding Protein Cytoplasm/metabolism DNA Primers/genetics DNA-Binding Proteins/genetics,physiology Dimerization G-Box Binding Factors HeLa Cells Hepacivirus/pathogenicity Humans Mice Molecular Sequence Data Protein Binding Protein Structure, Quaternary Sequence Homology, Amino Acid Transcription Factors/chemistry,genetics,physiology Transcriptional Activation Viral Core Proteins/physiology
Chemicals
Basic-Leucine Zipper Transcription Factors CREB3 protein, human Cyclic AMP Response Element-Binding Protein DNA Primers DNA-Binding Proteins G-Box Binding Factors Transcription Factors Viral Core Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Jin D Y
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
Zhou Y
Chun A C
Kibler K V
Hou Y D
Kung H
Jeang K T
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.4.729
Email
dyjin@hkucc.hku.hk
Published
2000-02-15
Pages
729-40
Language
English
Region
England
NLM ID
8208664
PMCID
PMC305611
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.4.729 PMC Full Text View journal details
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