Nuclear survivin has reduced stability and is not cytoprotective
Nuclear survivin has reduced stability and is not cytoprotective
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DOI：
10.1074/jbc.m704461200
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发表时间：
2008-02-08
影响因子：
4.8
通讯作者：
Wheatley, Sally P.
中科院分区：
文献类型：
--
作者：
Connell, Claire M.;Colnaghi, Rita;Wheatley, Sally P.
Survivin是一种重要的有丝分裂蛋白，在许多癌症中过度表达，它的存在与对放射和化疗的抵抗力增强有关。在这里，我们证明了将Survivin送入细胞核以CDH1依赖的方式加速其降解，取消通常由其过度表达而赋予细胞的辐射抵抗，并在不影响其有丝分裂定位的情况下阻止Survivin抑制细胞凋亡。我们的数据表明，将Survivin靶向于细胞核提供了一种有效的方法将其从细胞中消除，并可能被证明是癌症治疗的一种新策略，特别是与放射治疗相结合。
Survivin is an essential mitotic protein that is overexpressed in many cancers, and its presence is correlated with increased resistance to radiation and chemotherapy. Here we demonstrate that sending survivin into the nucleus accelerates its degradation in a cdh1-dependent manner, abolishes the radio resistance normally conferred to cells by its overexpression, and prevents survivin from inhibiting apoptosis without affecting its mitotic localization. Our data suggest that targeting survivin to the nucleus provides an efficient means of eliminating it from the cell and may prove a novel strategy in cancer treatment, particularly in combination with radiotherapy.