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

• Published in: Cell cycle (Georgetown, Tex.) Vol. 6; no. 1; pp. 95 - 103
• Main Authors: Jackson II, Roger S., Cho, Yong-Jig, Stein, Susanne, Liang, Peng
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 01.01.2007
• Subjects: Adaptor Proteins, Signal Transducing - biosynthesis; Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cell Line, Tumor; Cercopithecus aethiops; COS Cells; Cycle; Fatty Acids, Unsaturated - pharmacology; Gene Targeting - methods; Humans; Landes; Organogenesis; Proteins; Subcellular Fractions - metabolism; Transcriptional Activation - physiology; Tumor Suppressor Protein p53 - physiology
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.6.1.3665

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.