Kim Ji Young, Chung Jin-Yong, Lee Seung Gee, Kim Yoon-Jae, Park Ji-Eun, Yoo Ki Soo, Yoo Young Hyun, Park Young Chul, Kim Byeong Gee, Kim Jong-Min
Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, Busan 602-714, Republic of Korea.
Biochem Biophys Res Commun. 2006 Dec 1;350(4):949-54. doi: 10.1016/j.bbrc.2006.09.143. Epub 2006 Oct 5.
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.
Smac/DIABLO 由线粒体在凋亡刺激下释放，被认为可拮抗凋亡抑制蛋白的功能。最近研究表明，与 XIAP 一样，Survivin 可能与 Smac/DIABLO 相互作用。然而，它们作用的精确机制和细胞定位尚未确定。我们首次报道，在多西他赛处理 DU145 前列腺癌细胞导致 G2/M 期阻滞从而引发凋亡的过程中，Smac/DIABLO 转位至细胞核并与 Survivin 在有丝分裂纺锤体处共定位。我们的数据表明，Smac/DIABLO 与 Survivin 在细胞核内的相互作用是抑制 Survivin 在多西他赛诱导的凋亡中抗凋亡功能的重要步骤。这表明细胞内 Smac/DIABLO 和 Survivin 水平之间的平衡对于紫杉烷处理的癌细胞的细胞命运可能至关重要。
