Temasek Life Sciences Laboratory, National University of Singapore, Singapore, Singapore.
Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
PLoS One. 2020 May 13;15(5):e0232755. doi: 10.1371/journal.pone.0232755. eCollection 2020.
The quality control of intracellular proteins is achieved by degrading misfolded proteins which cannot be refolded by molecular chaperones. In eukaryotes, such degradation is handled primarily by the ubiquitin-proteasome system. However, it remained unclear whether and how protein quality control deploys various deubiquitinases. To address this question, we screened deletions or mutation of the 20 deubiquitinase genes in Saccharomyces cerevisiae and discovered that almost half of the mutations slowed the removal of misfolded proteins whereas none of the remaining mutations accelerated this process significantly. Further characterization revealed that Ubp6 maintains the level of free ubiquitin to promote the elimination of misfolded cytosolic proteins, while Ubp3 supports the degradation of misfolded cytosolic and ER luminal proteins by different mechanisms.
细胞内蛋白质的质量控制是通过降解无法被分子伴侣重新折叠的错误折叠蛋白质来实现的。在真核生物中，这种降解主要由泛素-蛋白酶体系统处理。然而，蛋白质质量控制是否以及如何利用各种去泛素化酶仍不清楚。为了解决这个问题，我们筛选了酿酒酵母中 20 个去泛素化酶基因的缺失或突变，发现几乎一半的突变会减缓错误折叠蛋白质的去除，而其余突变则没有明显加速这一过程。进一步的特征分析表明，Ubp6 维持游离泛素的水平以促进错误折叠胞质蛋白的清除，而 Ubp3 通过不同的机制支持错误折叠胞质和内质网腔蛋白的降解。
