Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto, 860-8555, Japan.
Mol Cell Biochem. 2018 Nov;448(1-2):155-164. doi: 10.1007/s11010-018-3322-z. Epub 2018 Feb 13.
We have demonstrated that the loss of programmed cell death 4 (Pdcd4), a translation inhibitor, induces apoptosis; however, when, where, and how Pdcd4 decreases in response to apoptotic stimuli and, conversely, exerts the anti-apoptotic function within normal cells are incompletely understood. Endogenous Pdcd4 was present in both the cytoplasm and nucleus of cells that survived. In cells that had committed to die by apoptotic stimuli, cytoplasmic Pdcd4 was lost more slowly than was nuclear Pdcd4; eventually, Pdcd4 remaining in the cytoplasm was lost and then apoptotic events were induced. Treatment with leptomycin B led to blocked nuclear export of Pdcd4 in cells exposed to apoptotic stimuli, assuming its translocation from the nucleus to the cytoplasm in the early phase of apoptotic processes. In cells overexpressing Pdcd4, the protein localized exclusively cytoplasmic. Overexpression of Pdcd4 resulted in reduced incidence of apoptosis in cells exposed to apoptotic stimuli compared to control cells. In addition, the expression of Procaspase-3, which is translated from the mRNA targeted by Pdcd4, was suppressed in cells overexpressing Pdcd4. Thus, the localization of Pdcd4 to the cytoplasm may be responsible for the suppression of the target mRNA translation and apoptosis.
我们已经证明，程序性细胞死亡因子 4（Pdcd4）的缺失会诱导细胞凋亡，Pdcd4 是一种翻译抑制剂。然而，对于凋亡刺激下 Pdcd4 的减少的时间、地点和方式，以及在正常细胞中发挥抗凋亡功能的机制，我们还不完全了解。存活细胞的细胞质和细胞核中都存在内源性 Pdcd4。在受到凋亡刺激而死亡的细胞中，细胞质中的 Pdcd4 比核中的 Pdcd4 丢失得更慢；最终，细胞质中残留的 Pdcd4 丢失，然后诱导凋亡事件。用莱普霉素 B 处理可导致暴露于凋亡刺激的细胞中 Pdcd4 的核输出受阻，假设其在凋亡过程的早期从细胞核易位到细胞质。在过表达 Pdcd4 的细胞中，该蛋白仅定位于细胞质。与对照细胞相比，过表达 Pdcd4 可降低暴露于凋亡刺激的细胞中凋亡的发生率。此外，过表达 Pdcd4 可抑制 Procaspase-3 的表达，Procaspase-3 是由 Pdcd4 靶向的 mRNA 翻译而来的。因此，Pdcd4 定位于细胞质可能是抑制靶 mRNA 翻译和凋亡的原因。
