Accumulation of polyubiquitinated proteins: A consequence of early inactivation of the 26S proteasome

• Published in: Free radical biology & medicine 2020-11, Vol.160, p.293-302
• Main Authors: Reeg, Sandra, Castro, José P., Hugo, Martin, Grune, Tilman
• Format: Article
• Language: English
• Subjects: Oxidative stress; Polyubiquitination; Proteasome; Protein oxidation; Ubiquitin
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2020.08.008

The proteasomal degradation system is one of the most important protein degradation systems in the cytosol and nucleus. This system is present in two major forms: the ATP-stimulated 26S/30 S proteasome or the ATP-independent 20S core proteasome. While the first recognize ubiquitin-tagged target proteins and degrade them, the 20S proteasome works also independent from ATP, but requires partially unfolded substrates. While the role of the proteasome in the selective removal of oxidized proteins is undoubted, the debate about a selective ubiquitination of oxidized proteins is still ongoing. Here we demonstrate, that under some conditions of oxidative stress an accumulation of oxidized and of K48-ubiquitinated proteins occurs. However, the removal of oxidized proteins seems not to be linked to ubiquitination. In further experiments, we could show that the accumulation of ubiquitinated proteins under certain oxidative stress conditions is rather a result of a different sensitivity of the 26S proteasome and the ubiquitination machinery towards oxidants. [Display omitted] •Oxidative stress leads to a temporary presence of K48-polyubiquitinated proteins.•Polyubiquitination of proteins after oxidative stress is not selective for oxidized proteins.•The 26S proteasome has a higher sensitivity towards oxidative inactivation, compared to the ubiquitination machinery.