CYFIP2, a direct p53 target, is leptomycin-B sensitive.
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.
Jackson
Roger S
RS
Vanderbilt-Ingram Comprehensive Cancer Center, Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-6840, USA.
Cho
Yong-Jig
YJ
Stein
Susanne
S
Liang
Peng
P
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D013347:Subcellular Fractions / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; C518673:CYFIP2 protein, human; D005231:Fatty Acids, Unsaturated; D016159:Tumor Suppressor Protein p53; C038753:leptomycin B