GSE15780
Interplay between c-Jun and TAp73a/ß contributes to the apoptosis-survival balance
The p53-family member p73 functions in various cellular signaling pathways and can have tumor suppressor properties. Several isoforms of p73 exist that differ considerably in their function. Whereas the functions of the N-terminal isoforms (TA and ?Np73) and their opposing pro- and anti-apoptotic roles became evident, the functional differences of the distinct C-terminal spliceforms of TAp73 have remained unclear. Here, we characterized the genomic binding sites for TAp73a and TAp73ß and identified a specific p73 consensus binding-motif. Furthermore, an AP1 motif is strongly enriched close to binding sites for TAp73a. These AP1 motif-containing target genes are selectively upregulated by TAp73a, while their mRNA expression is repressed upon TAp73ß induction. Recruitment of c-Jun to the respective AP1 sites was impaired upon TAp73ß expression in part due to downregulation of c-Jun. We show that several of these AP1-site containing TAp73a-induced genes reduce on apoptosis-induction suggesting an underlying molecular mechanism for the observed functional differences between TAp73a and TAp73ß. Overall design: ChIP-seq and RNA-seq profiles of TAp73alpha, TAp73beta and p53 stably transfected in human osteosarcoma Saos cells