Nakamura Yohko, Ozaki Toshinori, Niizuma Hidetaka, Ohira Miki, Kamijo Takehiko, Nakagawara Akira
Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba, Japan.
Biochem Biophys Res Commun. 2007 Mar 23;354(4):892-8. doi: 10.1016/j.bbrc.2007.01.057. Epub 2007 Jan 22.
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.
p53是多种细胞应激反应的关键调节因子。在人类神经母细胞瘤中，p53很少发生突变，且在细胞质中异常表达。在本研究中，我们在神经母细胞瘤SK-N-AS细胞中鉴定出一种新型的缺失其COOH末端区域的p53突变体。p53在顺铂（CDDP）作用下积累，从而促进携带野生型p53的神经母细胞瘤SH-SY5Y细胞凋亡，而SK-N-AS细胞未发生凋亡。我们在SK-N-AS细胞中发现了另一种缺失部分寡聚化结构域和核定位信号的p53（p53DeltaC）。p53DeltaC主要在细胞质中表达，并丧失了反式激活功能。此外，SK-N-AS细胞中p53基因座的3'部分发生了纯合缺失。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。
