Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), 14558 Nuthetal, Germany.
Servicio de Proteómica, Centro de Biología Molecular "Severo Ochoa (CBSMO), Consejo Superior de Investigaciones Científicas (CSIC) - UAM, E-28049 Madrid, Spain.
Redox Biol. 2018 Jun;16:123-128. doi: 10.1016/j.redox.2018.02.016. Epub 2018 Feb 22.
Under oxidative stress 26S proteasomes suffer reversible disassembly into its 20S and 19S subunits, a process mediated by HSP70. This inhibits the degradation of polyubiquitinated proteins by the 26S proteasome and allows the degradation of oxidized proteins by a free 20S proteasome. Low fluxes of antimycin A-stimulated ROS production caused dimerization of mitochondrial peroxiredoxin 3 and cytosolic peroxiredoxin 2, but not peroxiredoxin overoxidation and overall oxidation of cellular protein thiols. This moderate redox imbalance was sufficient to inhibit the ATP stimulation of 26S proteasome activity. This process was dependent on reversible cysteine oxidation. Moreover, our results show that this early inhibition of ATP stimulation occurs previous to particle disassembly, indicating an intermediate step during the redox regulation of the 26S proteasome with special relevance under redox signaling rather than oxidative stress conditions.
在氧化应激下，26S 蛋白酶体可逆地解组装为 20S 和 19S 亚基，这一过程由 HSP70 介导。这抑制了 26S 蛋白酶体对多泛素化蛋白的降解，并允许自由的 20S 蛋白酶体降解氧化蛋白。低通量的抗霉素 A 刺激的 ROS 产生导致线粒体过氧化物酶 3 和胞质过氧化物酶 2 的二聚化，但不会导致过氧化物酶过度氧化和细胞蛋白巯基的整体氧化。这种适度的氧化还原失衡足以抑制 ATP 对 26S 蛋白酶体活性的刺激。这个过程依赖于半胱氨酸的可逆氧化。此外，我们的结果表明，这种对 ATP 刺激的早期抑制发生在颗粒解组装之前，这表明在 26S 蛋白酶体的氧化还原调节中有一个中间步骤，在氧化还原信号而不是氧化应激条件下具有特殊意义。
