Cloning and Characterization of the Novel Chimeric Gene p53/FXR2 in the Acute Megakaryoblastic Leukemia Cell Line CMK11-5

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  • Kanezaki Rika
    Department of Pediatrics, Hirosaki University School of Medicine
  • Toki Tsutomu
    Department of Pediatrics, Hirosaki University School of Medicine
  • Xu Gang
    Department of Pediatrics, Hirosaki University School of Medicine Department of Pediatrics, 2nd Affiliated Hospital of China Medical University
  • Narayanan Ramswamy
    Department of Biological Sciences, Florida Atlantic University
  • Ito Etsuro
    Department of Pediatrics, Hirosaki University School of Medicine

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Abstract

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 p21WAF-1/CIP1, in CMK11-5 cells, and transient transfection analysis showed that the p53/FXR2 protein failed to transactivate the p21WAF-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.

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