ITAV-CNRS USR 3505 IPBS-UPS, 1 place Pierre Potier, 31106 Toulouse, France.
Molecules. 2020 May 18;25(10):2352. doi: 10.3390/molecules25102352.
Protein degradation is tightly regulated inside cells because of its utmost importance for protein homeostasis (proteostasis). The two major intracellular proteolytic pathways are the ubiquitin-proteasome and the autophagy-lysosome systems which ensure the fate of proteins when modified by various members of the ubiquitin family. These pathways are tightly interconnected by receptors and cofactors that recognize distinct chain architectures to connect with either the proteasome or autophagy under distinct physiologic and pathologic situations. The degradation of proteasome by autophagy, known as proteaphagy, plays an important role in this crosstalk since it favours the activity of autophagy in the absence of fully active proteasomes. Recently described in several biological models, proteaphagy appears to help the cell to survive when proteostasis is broken by the absence of nutrients or the excess of proteins accumulated under various stress conditions. Emerging evidence indicates that proteaphagy could be permanently activated in some types of cancer or when chemoresistance is observed in patients.
蛋白质降解在细胞内受到严格调控，因为它对蛋白质的动态平衡（蛋白质稳态）至关重要。两种主要的细胞内蛋白水解途径是泛素-蛋白酶体和自噬-溶酶体系统，它们确保了蛋白质在被泛素家族的各种成员修饰后的命运。这些途径通过受体和辅助因子紧密连接，这些受体和辅助因子识别不同的链结构，以便在不同的生理和病理情况下与蛋白酶体或自噬连接。自噬对蛋白酶体的降解，即自噬性蛋白降解，在这种串扰中起着重要作用，因为它有利于在没有完全活性的蛋白酶体的情况下自噬的活性。在几种生物模型中最近被描述，自噬性蛋白降解似乎有助于细胞在缺乏营养或在各种应激条件下积累过多蛋白质时，当蛋白质稳态被破坏时存活。新出现的证据表明，自噬性蛋白降解在某些类型的癌症或在观察到患者的化疗耐药性时可能会被永久激活。
