A novel apoptotic pathway dependent on ribosome

目前公认的诱导细胞凋亡的途径主要有两种，即外源性或受体介导的途径和内源性或线粒体途径。内在途径是细胞死亡最常见的途径，可被各种刺激激活。这些刺激引起线粒体外膜的通透性和细胞色素c的释放。细胞色素c与凋亡蛋白酶激活因子（Apaf-1）和casepase-9前分子结合，形成caspase-激活复合物，即凋亡体。外源性途径通过特定死亡配体与其细胞表面死亡受体的相互作用而激活。我们发现αNAC（新生多肽相关复合体）与细胞凋亡有关。αNAC在核糖体新生链的结合和保护中起着重要作用。我们认为可能存在与核糖体相关的诱导细胞凋亡的其他途径，并增加了两条主要途径。本研究表明，siRNA诱导αNAC耗竭可诱导细胞凋亡，其途径可能与内质网应激有关。

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.