Fig. 4
From: Redox regulation: mechanisms, biology and therapeutic targets in diseases
Redox regulation of proteolysis. Under normoxia, Cys2 enzymatically reacts with molecular oxygen (O2), followed by arginylation mediated by ATE1. The resulting Arginyl-CysO2(H) is recognized by the UBR boxes of N-recognins UBR1 and UBR2, leading to K48-linked ubiquitylation and subsequent proteasomal degradation. During acute hypoxia, oxidation of Nt-Cys2 is either delayed or disrupted, resulting in the stabilization of RGS proteins, which participate in cellular responses to hypoxia. In the context of chronic hypoxia and oxidative stress, Nt-Cys undergoes chemical oxidation by ROS to form CysO3(H). Subsequently, ATE1 catalyzes the arginylation of CysO3(H), which assembles K63-linked Ub chains on the substrates and degraded by the autophagy-lysosomal pathway
