The c-jun proto-oncogene down-regulates the rat alpha-fetoprotein promoter in HepG2 hepatoma cells without binding to DNA.

The Journal of Biological Chemistry
Brigitte Bois-JoyeuxJ L Danan

Abstract

The effects of a phorbol ester (TPA) and of members of the Jun and Fos oncoprotein family on the activity of the rat alpha-fetoprotein (AFP) promoter were checked by using transient expression experiments in HepG2 hepatoma cells. TPA blocked the activity of the rat AFP promoter in a dose-dependent manner. Overexpression of c-Jun specifically repressed the rat AFP promoter but not the albumin promoter. JunB and JunD were poorer inhibitors. c-Fos expression did not potentiate the negative effect of Jun. The Jun-induced repression does not require binding of c-Jun to the AFP promoter. DNase 1 footprinting experiments did not display any high affinity binding site for Jun on the AFP promoter. Integrity of the c-Jun DNA binding domain is not required for the c-Jun protein to block the AFP promoter. The N-terminal part of Jun, which contains the activating domain, is responsible for the repression as shown by using Jun-Gal4 chimera. Jun likely exerts its negative control on the AFP promoter via protein-protein interactions with a not yet identified trans-activating factor within the -134 to +6 region or with a component of the general machinery of transcription. Jun proteins can thus be key intermediates in regulatory cascades which ...Continue Reading

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Citations

Feb 10, 1998·International Journal of Cancer. Journal International Du Cancer·T L EraiserG I Abelev
Sep 2, 1999·Prostaglandins, Leukotrienes, and Essential Fatty Acids·B Bois-JoyeuxJ L Danan
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Aug 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Zhifang XieWeiping J Zhang
Jul 16, 2015·Scientific Reports·Hai ZhangWeiping J Zhang
Jun 9, 2005·Molecular Endocrinology·Caroline ChauvetJean-Louis Danan
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