摘要
作为一个批评 apoptosis 刽子手， caspase-3 变得激活然后进入原子核施加它的功能。然而，活跃 caspase-3 的这个原子条目的分子的机制仍然是未知的。在这研究，我们表明 caspase-3 怀有 crm-1-independent 在它的小子单元的原子出口信号(NES ) 。把 reverse-caspase-3 用作学习模型，我们发现在 caspase-3 的 NES 的功能没被 conformational 变化在导致的 caspase-3 激活期间扰乱。破坏劈开活动或 p3 识别地点的变化在活跃 caspase-3 的原子入口导致了一个缺点。我们提供活跃 caspase-3 的调停 p3 的特定的劈开活动废除了 NES 的功能的证据。在结论，我们的结果证明在 caspase-3 激活期间， NES 是组成地在场的。调停 p3 的特定的劈开活动在 caspase-3 废除 NES 功能，因此便于活跃 caspase-3 的原子入口。
As a critical apoptosis executioner, caspase-3 becomes activated and then enters into the nucleus to exert its function. However, the molecular mechanism of this nuclear entry of active caspase-3 is still unknown. In this study, we revealed that easpase-3 harbors a crm-l-independent nuclear export signal （NES） in its small subunit. Using reversecaspase-3 as the study model, we found that the function of the NES in caspase-3 was not disturbed by the conformational changes during induced caspase-3 activation. Mutations disrupting the cleavage activity or p3-recognition site resulted in a defect in the nuclear entry of active caspase-3. We provide evidence that the p3-mediated specific cleavage activity of active caspase-3 abrogated the function of the NES. In conclusion, our results demonstrate that during caspase-3 activation, NES is constitutively present, p3-mediated specific cleavage activity abrogates the NES function in caspase-3, thus facilitating the nuclear entry of active caspase-3.
基金
Supplementary information is linked to the online version of the paper on the Cell Research website.Acknowledgments We thank Prof Jian Wang （Shanghai University, Shanghai） for his valuable revision and discussion. This work was supported by grants from the National Natural Science Foundation of China （30700411）, Shenzhen Bureau of Science Technology and Information （SZKJ-2006018, SZKJ-2007012）, Shenzhen Nanshan Bureau of Science Technology and Information （2008036） and Shenzhen Key Laboratory Advancement Scheme.
