RRC ID 42673
Author Kanezaki R, Toki T, Xu G, Narayanan R, Ito E.
Title Cloning and characterization of the novel chimeric gene p53/FXR2 in the acute megakaryoblastic leukemia cell line CMK11-5.
Journal Tohoku J Exp Med
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 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.
Volume 209(3)
Pages 169-80
Published 2006-7-1
DOI 10.1620/tjem.209.169
PII JST.JSTAGE/tjem/209.169
PMID 16778363
MeSH Animals Base Sequence COS Cells Cell Line, Tumor Cell Transformation, Neoplastic Chlorocebus aethiops Cloning, Molecular Cyclin-Dependent Kinase Inhibitor p21 / metabolism Etoposide / pharmacology Gene Expression Profiling Genes, p53 / genetics* Humans Leukemia, Megakaryoblastic, Acute / genetics* Mice Molecular Sequence Data Mutant Chimeric Proteins / genetics* NIH 3T3 Cells RNA-Binding Proteins / genetics* Topoisomerase II Inhibitors
IF 1.441
Times Cited 2
WOS Category MEDICINE, RESEARCH & EXPERIMENTAL
Resource
Human and Animal Cells NIH3T3-3-4(RCB1862)