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

Yohko Nakamura, Toshinori Ozaki, Hidetaka Niizuma, Miki Ohira, Takehiko Kamijo, Akira Nakagawara

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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 (p53ΔC) lacking a part of oligomerization domain and nuclear localization signals in SK-N-AS cells. p53ΔC 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.

Original languageEnglish
Pages (from-to)892-898
Number of pages7
JournalBiochemical and biophysical research communications
Volume354
Issue number4
DOIs
Publication statusPublished - 2007 Mar 23
Externally publishedYes

Keywords

  • Apoptosis
  • Cisplatin
  • Homozygous deletion
  • Neuroblastoma
  • p53

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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