Survivin: Key regulator of mitosis and apoptosis and novel target for cancer therapeutics
Survivin: Key regulator of mitosis and apoptosis and novel target for cancer therapeutics
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DOI：
10.1158/1078-0432.ccr-08-0746
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发表时间：
2008-08-15
影响因子：
11.5
通讯作者：
Giles, Francis J.
中科院分区：
文献类型：
--
作者：
Mita, Alain C.;Mita, Monica M.;Giles, Francis J.
生存素是凋亡蛋白抑制剂家族的成员，是有丝分裂和程序性细胞死亡的关键调节因子。最初，survivin 被描述为 caspase-9 的抑制剂。然而，近年来的研究表明，生存素在癌症发病机制中的作用不仅限于抑制细胞凋亡，还涉及有丝分裂纺锤体检查点的调节以及促进血管生成和化疗耐药。生存素基因表达受到野生型 p53 的转录抑制，并且可以通过多种机制在癌症中失调，包括基因扩增、低甲基化、启动子活性增加和 p53 功能丧失。本文综述了生存素在调节细胞凋亡、促进肿瘤发生等方面的多种功能，以及生存素抑制剂作为新型抗癌治疗策略的开发。
Survivin, a member of the family of inhibitor of apoptosis proteins, functions as a key regulator of mitosis and programmed cell death. Initially, survivin was described as an inhibitor of caspase-9. However, over the last years, research studies have shown that the role of survivin in cancer pathogenesis is not limited to apoptosis inhibition but also involves the regulation of the mitotic spindle checkpoint and the promotion of angiogenesis and chemoresistance. Survivin gene expression is transcriptionally repressed by wild-type p53 and can be deregulated in cancer by several mechanisms, including gene amplification, hypomethylation, increased promoter activity, and loss of p53 function. This article reviews the multiple functions of survivin in the regulation of apoptosis, the promotion of tumorigenesis, and the development of survivin inhibitors as a novel anticancer therapeutic strategy.