Activation of RB/E2F signaling pathway is required for the modulation of hepatitis C virus core protein-induced cell growth in liver and non-liver cells.
Cell Signal
; 16(12): 1375-85, 2004 Dec.
Article
in En
| MEDLINE
| ID: mdl-15381253
ABSTRACT
Hepatitis C virus (HCV) core protein is a multifunctional protein that affects transcription and cell growth in vitro and in vivo. Here, we confirm the proliferative activities of core protein in liver and non-liver cells and delineate part of the mechanism whereby core protein promotes cell growth. We show that core protein suppresses the expression of tumor suppressor protein p53 and cyclin-dependent kinase (CDK) inhibitor p21 and enhances the activation of cyclin-dependent kinase 2 (CDK2), the phosphorylation of retinoblastoma (Rb), the activation of the transcription factor E2F-1, and the expression of E2F-1 and S phase kinase-interacting protein 2 (SKP2) genes. Pretreatment of core protein-expressing cells with the inhibitor of CDK2, Butyrolactone I, abolished the phosphorylation of Rb, the activation of E2F-1, and inhibited the expression of E2F-1 gene and cell growth induced. Consistent with these findings, we define a new signaling pathway whereby the HCV core protein mediates cell growth in infected cells.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transcription Factors
/
4-Butyrolactone
/
Hepacivirus
/
Cell Cycle Proteins
/
DNA-Binding Proteins
/
Liver
Limits:
Humans
Language:
En
Journal:
Cell Signal
Year:
2004
Document type:
Article
Affiliation country:
Germany