Apoptin特异性诱导肿瘤细胞凋亡的分子机制  

Molecular Mechanism of Specific Induction of Apoptosis in Tumor Cells by Apoptin

作　　者：王清明[1] 贺福初[1] 

机构地区：[1]军事医学科学院放射医学研究所基因组学与蛋白质组学研究室,北京100850

出　　处：《癌症》2005年第4期509-512,共4页Chinese Journal of Cancer

摘　　要：Apoptin是一种来源于鸡贫血病毒的小蛋白,能特异性诱导肿瘤细胞和转化细胞凋亡,而对正常细胞无凋亡诱导作用。Apoptin的肿瘤细胞特异性与其在细胞中的亚细胞定位有关,在转化或肿瘤细胞中,Apoptin定位于细胞核,而在正常细胞中定位于细胞质。Apoptin的磷酸化决定其核定位,在肿瘤细胞中,Apoptin被磷酸化,磷酸化的Apoptin进入细胞核,并诱导细胞凋亡。Apoptin诱导的细胞凋亡不依赖p53,不为bcl鄄2、bcl鄄xL的过表达所抑制,但Apoptin诱导的快速凋亡效应需要caspase鄄3的活化。Apoptin具有很强的形成聚合体的倾向,在细胞内表达的Apoptin以多聚体形式存在,但多聚体的形成和解聚并不是其诱导凋亡所必需的。Apoptin诱导细胞凋亡的功能可能与其DNA结合能力密切相关。Apoptin, a small protein derived from chicken anemia virus, can spec ifically induce apoptosis in transformed cells or tumor cells, but not in normal cells. The tumor specificity of Apoptin relates to its subcellular localization . In transformed cells or tumor cells, Apoptin migrates to the nuclei, whereas i n non-transformed cells, it remains mainly within the cytoplasm. Phosphorylation is responsible for the nuclear localization of Apoptin. In tumor cells, Apoptin is phosphorylated, then translocates into the nuclei, and induces cell apoptosi s. Apoptin-induced apoptosis does not depend on functional p53, and can't be inh ibited by overexpression of Bcl-2 and Bcl-xL, but caspase-3 activation is necess ary for Apoptin-induced rapid apoptosis. Apoptin has a strong tendency to aggreg ate, and exists as aggregates in living cells, but in vivo formation and dissoci ation of the aggregates are not required for apoptosis-inducing activity of Apop tin. It is possible that Apoptin's ability to bind DNA closely relates to its ab ility to induce apoptosis.

关 键 词：APOPTIN 凋亡 核定位 肿瘤 

分 类 号：R730.5[医药卫生—肿瘤]