Nuclear survivin has reduced stability and is not cytoprotective

被引：70

作者：

Connell, Claire M. ^{[1
]}

Colnaghi, Rita ^{[1
]}

Wheatley, Sally P. ^{[1
]}

机构：

[1] Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2008年 / 283卷 / 06期

基金：

英国医学研究理事会;

关键词：

SPLICE VARIANTS; SUBCELLULAR-LOCALIZATION; AURORA-B; DEGRADATION; PROTEIN; APOPTOSIS; MITOSIS; EXPORT; PHOSPHORYLATION; EXPRESSION;

D O I：

10.1074/jbc.M704461200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：3289 / 3296

页数：8

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