Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Japan.
Cell Death Differ. 2012 Apr;19(4):573-81. doi: 10.1038/cdd.2011.126. Epub 2011 Sep 30.
The programmed cell death 4 (Pdcd4), a translation inhibitor, plays an essential role in tumor suppression, but its role in apoptosis remains unclear. Here we show that Pdcd4 is a critical suppressor of apoptosis by inhibiting the translation of procaspase-3 mRNA. Pdcd4 protein decreased more rapidly through microRNA-mediated translational repression following apoptotic stimuli than did the activation of procaspase-3, cleavage of poly(ADP)ribose polymerase (PARP) by active caspase-3, and nuclear fragmentation. Strikingly, the loss of Pdcd4 by the specific RNA interference increased procaspase-3 expression, leading to its activation and PARP cleavage even without apoptotic stimuli, and sensitized the cells to apoptosis. Thus, our findings provide insight into a novel mechanism for Pdcd4 as a regulator of apoptosis.
程序性细胞死亡因子 4（Pdcd4）是一种翻译抑制剂，在肿瘤抑制中发挥着重要作用，但它在细胞凋亡中的作用尚不清楚。在这里，我们发现 Pdcd4 通过抑制前胱天蛋白酶-3 mRNA 的翻译，成为细胞凋亡的关键抑制因子。在凋亡刺激后，Pdcd4 蛋白通过 microRNA 介导的翻译抑制迅速减少，而前胱天蛋白酶-3 的激活、活性胱天蛋白酶-3对多聚（ADP-核糖）聚合酶（PARP）的切割以及核碎裂则相对较慢。引人注目的是，通过特异性 RNA 干扰使 Pdcd4 丢失会增加前胱天蛋白酶-3 的表达，导致其激活和 PARP 切割，即使没有凋亡刺激，也会使细胞对凋亡敏感。因此，我们的发现为 Pdcd4 作为细胞凋亡调节剂提供了新的机制见解。
