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Title: Functional characterization of a new p53 mutant generated by homozygous deletion in a neuroblastoma cell line

Abstract

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.

Authors:
 [1];  [1];  [1];  [1];  [1];  [2]
  1. Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan)
  2. Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260-8717 (Japan). E-mail: akiranak@chiba-cc.jp
Publication Date:
OSTI Identifier:
20979841
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 354; Journal Issue: 4; Other Information: DOI: 10.1016/j.bbrc.2007.01.057; PII: S0006-291X(07)00100-3; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BIOLOGICAL STRESS; CYTOPLASM; DNA; DNA DAMAGES; HUMAN POPULATIONS; MUTANTS; MUTATIONS

Citation Formats

Nakamura, Yohko, Ozaki, Toshinori, Niizuma, Hidetaka, Ohira, Miki, Kamijo, Takehiko, and Nakagawara, Akira. Functional characterization of a new p53 mutant generated by homozygous deletion in a neuroblastoma cell line. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.01.057.
Nakamura, Yohko, Ozaki, Toshinori, Niizuma, Hidetaka, Ohira, Miki, Kamijo, Takehiko, & Nakagawara, Akira. Functional characterization of a new p53 mutant generated by homozygous deletion in a neuroblastoma cell line. United States. doi:10.1016/j.bbrc.2007.01.057.
Nakamura, Yohko, Ozaki, Toshinori, Niizuma, Hidetaka, Ohira, Miki, Kamijo, Takehiko, and Nakagawara, Akira. Fri . "Functional characterization of a new p53 mutant generated by homozygous deletion in a neuroblastoma cell line". United States. doi:10.1016/j.bbrc.2007.01.057.
@article{osti_20979841,
title = {Functional characterization of a new p53 mutant generated by homozygous deletion in a neuroblastoma cell line},
author = {Nakamura, Yohko and Ozaki, Toshinori and Niizuma, Hidetaka and Ohira, Miki and Kamijo, Takehiko and Nakagawara, Akira},
abstractNote = {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.},
doi = {10.1016/j.bbrc.2007.01.057},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 354,
place = {United States},
year = {Fri Mar 23 00:00:00 EDT 2007},
month = {Fri Mar 23 00:00:00 EDT 2007}
}
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