Reference : c-JUN gene induction and AP-1 activity is regulated by a JNK-dependent pathway in hyp...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Human health sciences : Oncology
c-JUN gene induction and AP-1 activity is regulated by a JNK-dependent pathway in hypoxic HepG2 cells.
Minet, E. [> > > >]
Michel, G. [> > > >]
Mottet, Denis mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases >]
Piret, J. P. [ > > ]
Barbieux, A. [> > > >]
Raes, M. [> > > >]
Michiels, C. [> > > >]
Experimental Cell Research
Academic Press
Yes (verified by ORBi)
[en] Cell Hypoxia/physiology ; Cell Nucleus/metabolism ; DNA/metabolism ; DNA-Binding Proteins/metabolism ; Endothelial Growth Factors/genetics/metabolism ; Gene Expression Regulation ; Humans ; Hypoxia-Inducible Factor 1 ; Hypoxia-Inducible Factor 1, alpha Subunit ; Lymphokines/genetics/metabolism ; MAP Kinase Kinase Kinase 1 ; Nuclear Proteins/metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Proto-Oncogene Proteins c-jun/genetics/metabolism ; Transcription Factor AP-1/metabolism ; Transcription Factors ; Transcription, Genetic ; Transcriptional Activation ; Tumor Cells, Cultured ; Vascular Endothelial Growth Factor A ; Vascular Endothelial Growth Factors
[en] Hypoxia is an important pathophysiological stress that occurs during blood vessel injuries and tumor growth. It is now well documented that hypoxia leads to the activation of several transcription factors which participate in the adaptive response of the cells to hypoxia. Among these transcription factors, AP-1 is rapidly activated by hypoxia and triggers bFGF, VEGF, and tyrosine hydroxylase gene expression. However, the mechanisms of AP-1 activation by hypoxia are not well understood. In this report, we studied the events leading to AP-1 activation in hypoxia. We found that c-jun protein accumulates in hypoxic HepG2 cells. This overexpression is concomitant with c-jun phosphorylation and JNK activation. Moreover, we showed that AP-1 is transcriptionally active. We also observed that AP-1 transcriptional activity is inhibited by a MEKK1 dominant negative mutant. Moreover, the MEKK1 dominant negative mutant as well as deletion of the AP-1 binding sites within the c-jun promoter inhibited the c-jun promoter activation by hypoxia. All together, these results indicate that, in hypoxic HepG2 cells, AP-1 is activated through a JNK-dependent pathway and that it is involved in the regulation of the c-jun promoter, inducing a positive feedback loop on AP-1 activation via c-jun overexpression.
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS ; Fonds pour la Recherche dans l'Industrie et l'Agriculture, Belgique
Copyright 2001 Academic Press.

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