Weston Ross T, Puthalakath Hamsa
Department of Biochemistry, School of Molecular Sciences, La Trobe University, Bundoora, Australia.
Adv Exp Med Biol. 2010;687:65-77. doi: 10.1007/978-1-4419-6706-0_4.
In the eukaryotic cell, the endoplasmic reticulum (ER) plays an important role as the site of lipid synthesis, protein folding and protein maturation. Stringent regulation of redox and calcium homeostasis is paramount, failure of which leads accumulation of unfolded and aggregating proteins resulting in a condition known as ER stress. Eukaryotic cells deal with ER stress by eliciting the unfolded protein response (UPR). This pathway splits into two streams depending on the severity and longevity of the ER stress, where the cell must make a choice for the good of the organism between survival and programmed cell death. The BCL-2 family of proteins is central to the cell death arm of the UPR pathway. This chapter discusses the recent findings on the involvement of BCL-2 family members in the apoptotic process initiated by ER stress and a related process called autophagy. Understanding the molecular mechanisms involved in ER stress and autophagy could have a profound implications developing new therapies for many ER stress associated diseases and cancer.
在真核细胞中，内质网（ER）作为脂质合成、蛋白质折叠和蛋白质成熟的场所发挥着重要作用。严格调控氧化还原和钙稳态至关重要，若调控失败会导致未折叠和聚集蛋白的积累，从而引发一种称为内质网应激的状况。真核细胞通过引发未折叠蛋白反应（UPR）来应对内质网应激。根据内质网应激的严重程度和持续时间，该途径分为两个分支，细胞必须在生存和程序性细胞死亡之间做出有利于机体的选择。BCL-2蛋白家族在内质网应激反应途径的细胞死亡分支中起核心作用。本章讨论了BCL-2家族成员参与内质网应激引发的凋亡过程以及一个称为自噬的相关过程的最新研究发现。了解内质网应激和自噬所涉及的分子机制可能对开发许多内质网应激相关疾病和癌症的新疗法具有深远意义。
