Caruso Marie-Elaine, Chevet Eric
Team Avenir INSERM U889, Bordeaux, France.
Subcell Biochem. 2007;43:277-98. doi: 10.1007/978-1-4020-5943-8_13.
The endoplasmic reticulum (ER) is the first sub-cellular compartment encountered by secretory proteins en route to the plasma membrane. Newly synthesized secretory proteins translocate into the ER lumen and acquire their correct conformation prior to being exported to later compartments. When folding is not properly achieved, proteins accumulate in the ER due to resident quality control machineries and terminally misfolded proteins are ultimately degraded through the ER-associated degradation pathway. All these molecular machines function in a coordinated fashion to restore and maintain ER homeostasis. A fifth molecular machine plays a coordinating role in the ER. Indeed, the ER stress signaling machinery signals ER dysfunction to the rest of the cell and consequently integrates the functions of the four other molecular machines to improve their operation in stressful conditions. In this work, we have attempted to define the ER as a molecular biological system regulated by its own specific signaling pathways defined as the Unfolded Protein Response to delineate a systems biology approach of ER stress signaling.
内质网（ER）是分泌蛋白在运往质膜途中遇到的第一个亚细胞区室。新合成的分泌蛋白转运到内质网腔中，并在被输出到后续区室之前获得其正确的构象。当折叠未正确完成时，由于驻留的质量控制机制，蛋白质会在内质网中积累，最终错误折叠的蛋白质会通过内质网相关降解途径被降解。所有这些分子机器以协调的方式发挥作用，以恢复和维持内质网的稳态。第五种分子机器在内质网中起协调作用。实际上，内质网应激信号传导机制将内质网功能障碍信号传递给细胞的其他部分，从而整合其他四种分子机器的功能，以改善它们在应激条件下的运作。在这项工作中，我们试图将内质网定义为一个由其自身特定信号通路调节的分子生物学系统，该信号通路被定义为未折叠蛋白反应，以描绘内质网应激信号传导的系统生物学方法。
