1] Centre for Systems Medicine, Dublin 2, Ireland [2] Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, Dublin 2, Ireland.
Cell Death Dis. 2014 Jan 23;5(1):e1011. doi: 10.1038/cddis.2013.520.
Autophagic and proteasomal degradation constitute the major cellular proteolysis pathways. Their physiological and pathophysiological adaptation and perturbation modulates the relative abundance of apoptosis-transducing proteins and thereby can positively or negatively adjust cell death susceptibility. In addition to balancing protein expression amounts, components of the autophagic and proteasomal degradation machineries directly interact with and co-regulate apoptosis signal transduction. The influence of autophagic and proteasomal activity on apoptosis susceptibility is now rapidly gaining more attention as a significant modulator of cell death signalling in the context of human health and disease. Here we present a concise and critical overview of the latest knowledge on the molecular interplay between apoptosis signalling, autophagy and proteasomal protein degradation. We highlight that these three pathways constitute an intricate signalling triangle that can govern and modulate cell fate decisions between death and survival. Owing to rapid research progress in recent years, it is now possible to provide detailed insight into the mechanisms of pathway crosstalk, common signalling nodes and the role of multi-functional proteins in co-regulating both protein degradation and cell death.
自噬和蛋白酶体降解构成了主要的细胞内蛋白降解途径。它们的生理和病理生理适应和扰动调节了凋亡转导蛋白的相对丰度，从而可以正向或负向调节细胞死亡易感性。除了平衡蛋白质表达量外，自噬和蛋白酶体降解机制的成分还直接相互作用并共同调节凋亡信号转导。自噬和蛋白酶体活性对细胞死亡信号敏感性的影响作为人类健康和疾病中细胞死亡信号的重要调节剂，目前正受到越来越多的关注。在这里，我们对凋亡信号、自噬和蛋白酶体蛋白降解之间的最新分子相互作用进行了简明扼要的综述。我们强调，这三个途径构成了一个复杂的信号三角形，可以控制和调节死亡和存活之间的细胞命运决定。由于近年来研究进展迅速，现在可以详细了解途径串扰、共同信号节点以及多功能蛋白在共同调节蛋白降解和细胞死亡中的作用的机制。
