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c-Jun-mediated repression and transactivation of fibronectin
Yukio Hayashi1, Yuji Shino, Kengo Saito
1Department of Molecular Virology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Molecular Medicine Reports
|April 12, 2011
Summary
Human papillomavirus type 16 (HPV16) E6 protein influences fibronectin (FN) gene expression. This study reveals c-Jun can either activate or repress FN gene expression based on cellular context.
Area of Science:
- Molecular Biology
- Cell Biology
- Virology
Background:
- Fibronectin (FN) gene expression is regulated by various cellular factors.
- Human papillomavirus type 16 (HPV16) E6 protein is known to influence cellular gene expression.
- The transcription factor c-Jun plays a role in regulating gene expression, including FN.
Purpose of the Study:
- To investigate the role of c-Jun in regulating fibronectin (FN) gene expression.
- To elucidate the mechanism by which HPV16 E6 affects FN promoter activity.
- To determine the context-dependent effects of c-Jun on FN gene expression.
Main Methods:
- Northern and immunoblot analyses to assess c-Jun and FN expression levels.
- Luciferase reporter assays to measure FN promoter activity.
- Deletion and mutation analyses of the FN promoter, focusing on the cyclic AMP response element (CRE).
- Supershift assays to identify proteins binding to the CRE.
Main Results:
- c-Jun expression was enhanced in cells expressing HPV16 E6.
- Overexpression of c-Jun in mouse 10T1/2 cells showed an inverse correlation with FN expression, indicating repression.
- Repression of the FN promoter by c-Jun was dependent on the CRE site at -160.
- ATF-2 binding to the CRE was crucial for FN gene transactivation in HPV16 E6-expressing and c-Jun-overexpressing cells.
Conclusions:
- The transcription factor c-Jun can exhibit dual roles in regulating fibronectin gene expression, acting as either a transactivator or a repressor.
- The cellular context and interaction with factors like ATF-2 determine whether c-Jun activates or represses the FN gene.
- HPV16 E6 influences FN gene expression, at least partly, through the c-Jun/ATF-2 complex binding to the FN promoter's CRE.
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