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 (p53DeltaC) lacking a part of oligomerization domain and nuclear localization signals in SK-N-AS cells. p53DeltaC 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.affiliation: Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba, Japan.
authors.forename: Yohko
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ozaki
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Niizuma
authors.forename: Miki
authors.initials: M
authors.lastname: Ohira
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kamijo
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004249:DNA Damage; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53; D002945:Cisplatin