Bader Nicolle, Jung Tobias, Grune Tilman
University Hohenheim, Institute of Biological Chemistry and Nutrition, Department of Biofunctionality and Food Safety, 70593 Stuttgart, Germany.
Exp Gerontol. 2007 Sep;42(9):864-70. doi: 10.1016/j.exger.2007.03.010. Epub 2007 Apr 10.
The cellular proteome is in a dynamic state of synthesis and degradation. Degradation of extracellular proteins is mainly mediated non-specifically by the lysosomes or due to released proteases, while the proteolysis of intracellular including nuclear proteins is catalyzed by the ubiquitin-proteasome pathway. Furthermore, the proteasomal system is largely responsible for the removal of unfolded and oxidatively damaged proteins. Taking into account the role of ubiquitin and proteasome system in protein metabolism, studies of its spatial organization within the cell are of great importance. For the understanding of cellular, including nuclear, protein maintenance the distribution of the proteasomes in both the nucleus and the cytosol and their response upon oxidative stress is of great interest. Although, the functional diversity of the cells is ensured by the three dimensional organization of the nucleus, nuclear proteins are also prone to oxidation and have to be removed from the cellular environment by the nuclear proteasome. Interestingly, nuclear proteins are partly degraded within the nucleus, whereas some are exported from the nucleus to the cytosol. Proteasomes are transported unidirectionally from the cytoplasm to the nucleus with a possible countervail during mitosis. This review is focused largely on the specifics of cellular proteasome distribution and on nuclear protein maintenance under physiological and oxidative stress conditions.
细胞蛋白质组处于合成与降解的动态状态。细胞外蛋白质的降解主要由溶酶体非特异性介导或由释放的蛋白酶引起，而细胞内包括核蛋白的蛋白水解则由泛素 - 蛋白酶体途径催化。此外，蛋白酶体系统在很大程度上负责清除未折叠和氧化损伤的蛋白质。考虑到泛素和蛋白酶体系统在蛋白质代谢中的作用，研究其在细胞内的空间组织具有重要意义。为了理解细胞（包括细胞核）内的蛋白质维持情况，蛋白酶体在细胞核和细胞质中的分布及其对氧化应激的反应备受关注。虽然细胞核的三维组织确保了细胞的功能多样性，但核蛋白也容易被氧化，必须由核蛋白酶体从细胞环境中清除。有趣的是，核蛋白部分在细胞核内降解，而有些则从细胞核输出到细胞质。蛋白酶体从细胞质单向运输到细胞核，在有丝分裂期间可能存在抵消作用。本综述主要关注细胞蛋白酶体分布的细节以及生理和氧化应激条件下的核蛋白维持情况。
