Nuclear interaction of Smac/DIABLO with Survivin at G2/M arrest prompts docetaxel-induced apoptosis in DU145 prostate cancer cells

Nuclear interaction of Smac/DIABLO with Survivin at G2/M arrest prompts docetaxel-induced apoptosis in DU145 prostate cancer cells
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DOI:
10.1016/j.bbrc.2006.09.143
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发表时间:
2006-12-01
影响因子:
3.1
通讯作者:
Kim, Jong-Min
Kim, Jong-Min
中科院分区:
生物学4区
文献类型:
--
作者:
Kim, Ji Young;Chung, Jin-Yong;Kim, Jong-Min

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Smac/DIABLO由线粒体响应于凋亡刺激而释放,并且被认为拮抗凋亡蛋白的抑制剂的功能。最近,已经表明,像XIAP一样,Survivin可以潜在地与Smac/DIABLO相互作用。然而,其作用的确切机制和细胞定位尚未确定。我们首次报道了多西他赛治疗DU 145前列腺癌细胞导致G2/M期阻滞引起的细胞凋亡过程中,Smac/DIABLO易位至细胞核,并与Survivin共定位于有丝分裂纺锤体。我们的数据表明,Smac/DIABLO与存活素的核相互作用是抑制存活素在Doc诱导的细胞凋亡中的抗细胞凋亡功能的重要一步。这表明细胞Smac/DIABLO和Survivin水平之间的平衡可能对紫杉烷处理的癌细胞中的细胞命运至关重要。(c)2006年爱思唯尔公司All rights reserved.
Smac/DIABLO is released by mitochondria in response to apoptotic stimuli and is thought to antagonize the function of inhibitors of apoptosis proteins. Recently, it has been shown that, like XIAP, Survivin can potentially interact with Smac/DIABLO. However, the precise mechanisms and cellular location of their action have not been determined. We report for the first time that Smac/DIABLO translocates to the nucleus and is colocalized with Survivin at mitotic spindles during apoptosis resulting from G2/M arrest due to docetaxel treatment of DU145 prostate cancer cells. Our data demonstrate that the nuclear interaction of Smac/DIABLO with Survivin is an important step for suppressing the anti-apoptotic function of Survivin in Doc-induced apoptosis. This suggests that the balance between cellular Smac/DIABLO and Survivin levels could be critical for cellular destiny in taxane-treated cancer cells. (c) 2006 Elsevier Inc. All rights reserved.