A novel apoptotic pathway dependent on ribosome

依赖核糖体的新型凋亡途径

• 批准号: 17591967
• 负责人: HOTOKEZAKA Yuka
• 金额: $ 2.18万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591967/
• 关键词: αNAC; apoptosis; ribosome; ER stress; siRNA

It is now well recognized that there are two main pathway for the induction of apoptosis, the extrinsic or receptor-mediated pathway, and the intrinsic or mitochondria pathway. The intrinsic pathway is the most common pathway for cell death and can be activated by variety of stimuli. Theses stimuli cause the permeabilizaton of the mitochondria outer membrane and release of cytochrome c. Cytochrome c binds to the apoptosis protease-activationg factor (Apaf-1) and pro-casepase-9 molecules forming a caspase-activating complex, the apoptosome. The extrinsic pathway is activated by the interaction of a specific death ligand with its cell surface death receptors. We found that αNAC (nascent polypeptide-associated complex) is related with apoptosis. αNAC is known to play a role of binding of nascent chain emerging from ribosome and protecting them. We have an idea that there may be other pathway for the induction of apoptosis related with ribosome adding two main ones. Here we show that apoptosis is induced in cells by αNAC depletion using siRNA and the pathway of them may be related with ER (endoplasmic reticulum) stress.

现已认识到，诱导细胞凋亡主要有两种途径：外源性途径或受体介导途径，以及内源性途径或线粒体途径。内源性途径是最常见的细胞死亡途径，可被多种刺激激活。这些刺激导致线粒体外膜通透性和细胞色素c的释放。细胞色素c与凋亡蛋白激活因子(APAF-1)和前酪氨酸酶-9分子结合，形成caspase激活复合体--凋亡体。外源性途径是通过特定的死亡配体与其细胞表面死亡受体相互作用而激活的。我们发现αNAC(新生多肽相关复合体)与细胞凋亡有关。已知αNAC具有结合核糖体新生链并保护核糖体的作用。我们认为，可能还有其他与核糖体相关的诱导细胞凋亡的途径，另外还有两条主要途径。在这里，我们证明了αNAC耗尽通过siRNA诱导细胞凋亡，其途径可能与内质网应激有关。