Cloning and characterization of the novel chimeric gene p53/ FXR2 in the acute megakaryoblastic leukemia cell line CMK11-5.
The loss of p53 function is a key event in tumorigenesis. Inactivation of p53 in primary tumors and cell lines is mediated by several molecular mechanisms, including deletions and rearrangements. However, generation of a p53 fusion gene has not yet been reported. Here we report a novel p53/an autosomal homolog of the fragile X mental retardation ( FXR2) chimeric gene generated by an interstitial deletion. Western blot analyses have shown that the p53/ FXR2 protein is indeed expressed in a Down syndrome-related acute megakaryoblastic leukemia cell line, CMK11-5 cells. To investigate the properties of the p53/ FXR2 protein, we observed its subcellular localization. Flag-tagged expression vectors were transfected into COS-7 cells and the proteins were stained with an anti-Flag antibody. The p53/ FXR2 protein was expressed at high levels in the cytoplasm, whereas wild-type p53 and FXR2 were localized primarily in the nucleus and in the periphery of the nucleus, respectively. Treatment with a topoisomerase II inhibitor, VP16, failed to induce expression of a p53 target gene, the cyclin-dependent kinase inhibitor p21(WAF-1/ CIP1), in CMK11-5 cells, and transient transfection analysis showed that the p53/ FXR2 protein failed to transactivate the p21(WAF-1/ CIP1) promoter. These results suggest that the p53/ FXR2 fusion protein lacks the ability of wild-type p53 to function as a transcription factor. The p53/ FXR2 gene is the first reported p53 fusion gene.[1]References
- Cloning and characterization of the novel chimeric gene p53/FXR2 in the acute megakaryoblastic leukemia cell line CMK11-5. Kanezaki, R., Toki, T., Xu, G., Narayanan, R., Ito, E. Tohoku J. Exp. Med. (2006) [Pubmed]
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