Nucling recruits Apaf-1/pro-caspase-9 complex for the induction of stress-induced apoptosis
Nucling recruits Apaf-1/pro-caspase-9 complex for the induction of stress-induced apoptosis
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DOI：
10.1074/jbc.m402902200
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发表时间：
2004-09-24
影响因子：
4.8
通讯作者：
Fukui, K
中科院分区：
文献类型：
--
作者：
Sakai, T;Liu, L;Fukui, K
Nucling是从小鼠胚胎癌细胞中分离出来的一种新的蛋白质，在心肌分化过程中表达上调。我们在这里表明，Nucling被促凋亡刺激上调，并在细胞毒应激后诱导细胞凋亡中起重要作用。我们进一步证明了过表达的Nucling能够诱导细胞凋亡。在Nucling缺陷细胞中，APAF-1和细胞色素c的表达水平在细胞应激下都下调，这是一种名为凋亡体的促凋亡复合体的主要成分。缺乏Nucling也赋予细胞对凋亡压力的抵抗力。紫外光照射后，Nucling存在于APAF-1/Pro-caspase-9复合体中，提示Nucling可能是该复合体形成和维持的关键分子。Nucling诱导APAF-1转位到细胞核，从而将Nucling/APAF-1/Pro-caspase-9复合体分布到核部分。这些发现表明，Nucling在应激诱导的细胞凋亡过程中招募和运输凋亡体复合体。
Nucling is a novel protein isolated from murine embryonal carcinoma cells with an up-regulated expression during cardiac muscle differentiation. We show here that Nucling was up-regulated by proapoptotic stimuli and important for the induction of apoptosis after cytotoxic stress. We further demonstrated that overexpressed Nucling was able to induce apoptosis. In Nucling-deficient cells, the expression levels of Apaf-1 and cytochrome c, which are the major components of an apoptosis-promoting complex named apoptosome, were both down-regulated under cellular stress. A deficiency of Nucling also conferred resistance to apoptotic stress on the cell. After UV irradiation, Nucling was shown to reside in an Apaf-1/pro-caspase-9 complex, suggesting that Nucling might be a key molecule for the formation and maintenance of this complex. Nucling induced translocation of Apaf-1 to the nucleus, thereby distributing the Nucling/Apaf-1/pro-caspase-9 complex to the nuclear fraction. These findings suggest that Nucling recruits and transports the apoptosome complex during stress-induced apoptosis.