CYFIP2, a Direct p53 Target, is Leptomycin-B Sensitive

Abstract

A number of target genes for the tumor suppressor, p53, have been identified, however, the mechanisms that contribute to p53-dependent apoptosis remain to be fully elucidated. In a comprehensive screen for p53 target genes, we have identified Cytoplasmic FMR Interacting Protein 2 (CYFIP2) as a p53-inducible gene. Here we show that the CYFIP2 promoter contains a p53-responsive element that confers p53 binding as well as transcriptional activation of a heterologous reporter. Inducible expression of CYFIP2 is sufficient for caspase activation and cellular apoptosis, reminiscent of p53 activation. Together, these results suggest that CYFIP2 is a direct p53 target gene that may be part of a redundant network of genes responsible for p53-dependent apoptosis. In addition, the sensitivity of CYFIP2 protein subcellular localization to Leptomycin-B, a CRM-1/Exportin inhibitor, suggests that the biological functions of CYFIP2 may extend from the cytoplasmic compartment into the nucleus of the cell.