Journal
CELL CYCLE
Volume 6, Issue 1, Pages 95-103Publisher
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.6.1.3665
Keywords
differential display; p53 target gene; apoptosis; CYFIP2; PIR121; nucleocytoplasmic shuttling
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Funding
- NATIONAL CANCER INSTITUTE [R01CA105024, R01CA076960] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM008554] Funding Source: NIH RePORTER
- NCI NIH HHS [R01 CA76960, CA105024] Funding Source: Medline
- NIGMS NIH HHS [GM08554-7] Funding Source: Medline
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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.
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