Regulation of microtubule stability and mitotic progression by survivin.
Regulation of microtubule stability and mitotic progression by survivin.
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DOI：
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发表时间：
2002-05
期刊：
影响因子：
11.2
通讯作者：
A. Giodini;M. Kallio;N. Wall;G. Gorbsky;S. Tognin;P. Marchisio;M. Symons;D. Altieri
中科院分区：
文献类型：
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作者：
A. Giodini;M. Kallio;N. Wall;G. Gorbsky;S. Tognin;P. Marchisio;M. Symons;D. Altieri
Survivin是凋亡抑制因子（inhibitor of apoptosis，IAP）基因家族的成员，其在癌细胞中参与细胞活力的保持和有丝分裂的调节。在这里，我们发现，与对照注射细胞（前中期，21.5 +/- 3.3分钟;中期，18.9 +/- 4.5分钟; P < 0.01）相比，显微注射存活素多克隆抗体的HeLa细胞在前中期（31.5 +/- 6.9分钟）和中期（126.8 +/- 73.8分钟）表现出延迟的进展。注射存活素抗体的细胞显示短的有丝分裂纺锤体，微管严重耗尽，偶尔发生凋亡而不退出有丝分裂阻滞或其后。HeLa细胞中生存素的强制表达深刻地影响了微管动力学，在中期减少了极-极距离（8.57 +/- 0.21 μ m对10.58 +/- 0.19 μ m; P < 0.0001），并稳定了微管对诺考达唑诱导的体内解聚。这些数据表明，生存素的功能，在细胞分裂，以控制微管的稳定性和组装的一个正常的有丝分裂纺锤体。这种途径可能有助于检查点逃避，并促进癌症对化疗的耐药性。
Survivin is a member of the inhibitor of apoptosis (IAP) gene family, which has been implicated in both preservation of cell viability and regulation of mitosis in cancer cells. Here, we show that HeLa cells microinjected with a polyclonal antibody to survivin exhibited delayed progression in prometaphase (31.5 +/- 6.9 min) and metaphase (126.8 +/- 73.8 min), as compared with control injected cells (prometaphase, 21.5 +/- 3.3 min; metaphase, 18.9 +/- 4.5 min; P < 0.01). Cells injected with the antibody to survivin displayed short mitotic spindles severely depleted of microtubules and occasionally underwent apoptosis without exiting the mitotic block or thereafter. Forced expression of survivin in HeLa cells profoundly influenced microtubule dynamics with reduction of pole-to-pole distance at metaphase (8.57 +/- 0.21 microm versus 10.58 +/- 0.19 microm; P < 0.0001) and stabilization of microtubules against nocodazole-induced depolymerization in vivo. These data demonstrate that survivin functions at cell division to control microtubule stability and assembly of a normal mitotic spindle. This pathway may facilitate checkpoint evasion and promote resistance to chemotherapy in cancer.