Functional characterization of a new p53 mutant generated by homozygous deletion in a neuroblastoma cell line
Functional characterization of a new p53 mutant generated by homozygous deletion in a neuroblastoma cell line
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DOI：
10.1016/j.bbrc.2007.01.057
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发表时间：
2007-03-23
影响因子：
3.1
通讯作者：
Nakagawara, Akira
中科院分区：
文献类型：
--
作者：
Nakamura, Yohko;Ozaki, Toshinori;Nakagawara, Akira
P53是多种细胞应激的关键调节因子。在人类神经母细胞瘤中，p53很少发生突变并在细胞质中异常表达。在这项研究中，我们在神经母细胞瘤SK-N-AS细胞中发现了一个缺乏cooh末端区域的p53突变体。在携带野生型p53的神经母细胞瘤SH-SY5Y细胞中，p53对顺铂（CDDP）的反应会积累，从而促进细胞凋亡，而SK-N-AS细胞则不会发生凋亡。我们在SK-N-AS细胞中发现了另一个p53 （p53 Delta C）缺乏部分寡聚化结构域和核定位信号。p53 δ C在细胞质中大量表达，失去了转激活功能。此外，SK-N-AS细胞中p53位点的3'-部分被纯合删除。因此，我们目前的研究结果表明p53在某些神经母细胞瘤细胞的dna损伤反应中起重要作用，并且在dna结合域外寻找p53突变似乎很重要。(c) 2007爱思唯尔公司版权所有。
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.