Biochemical and Biophysical Research Communications, Vol.354, No.4, 892-898, 2007
Functional characterization of a new p53 mutant generated by homozygous deletion in a neuroblastoma cell line
p53 is a key modulator of a variety of cellular stresses. In human neuroblastomas, p53 is rarely mutated and aberrantly expressed in cytoplasm. In this study, we have identified a novel p53 mutant lacking its COOH-terminal region in neuroblastoma SK-N-AS cells. p53 accumulated in response to cisplatin (CDDP) and thereby promoting apoptosis in neuroblastoma SH-SY5Y cells bearing wild-type p53, whereas SK-N-AS cells did not undergo apoptosis. We found another p53 (p53 Delta C) lacking a part of oligomerization domain and nuclear localization signals in SK-N-AS cells. p53 Delta C was expressed largely in cytoplasm and lost the transactivation function. Furthermore, a 3'-part of the p53 locus was homozygously deleted in SK-N-AS cells. Thus, our present findings suggest that p53 plays an important role in the DNA-damage response in certain neuroblastoma cells and it seems to be important to search for p53 mutations outside DNA-binding domain. (c) 2007 Elsevier Inc. All rights reserved.