Role of c-Jun in the regulation of tumor suppressor p53 homologue, p73

Abstract

This study proposes for the first time that the transcription factor c-Jun stabilizes and activates p73. Genetic evidences consolidated the findings, as c-jun-/- cells are defective in p73 stabilization, transcriptional activation, and are resistant to cisplatin induced apoptosis. Upon introducing c-Jun in c-jun-/- cells restores p73 stabilization, activation, and sensitivity to cisplatin. UV radiation increases p73 levels in a variety of cell lines analyzed. In a parallel study, p73 increases AP-1 activity and it synergies with c-Jun to increase the expression of AP-1 dependent target genes. The NH2-terminus of p73 is necessary to synergizes with c-Jun. JNK-mediated c-Jun phosphorylation is required for its ability to co-operate with p73. Basal level of AP-1 activity was lowered by the dominant negative p73. Further, this study suggests the existence of a regulatory loop between the TA-p73/I?N-p73 and c-Jun. Collectively, this study indicates that c-Jun and p73 regulate each other in cell fate decisions.