Carbonylation‐Decarbonylation and Carbonylation‐Degradation Pathways in the Mechanism of Oxidant Signaling

Abstract

Reactive oxygen species (ROS) are recognized as mediators of cell signaling. Exact mechanisms of how ROS are involved in signaling processes, however, have not been defined. Our laboratory previously reported that ligand-receptor interactions can promote protein carbonylation and proposed that this type of protein oxidation is involved in the mechanism of ROS signaling. The present study provides evidence for the occurrence of two pathways that can be triggered in response to ligand/receptor-mediated protein carbonylation, namely (i) carbonylation-decarbonylation pathway and (ii) carbonylation-degradation pathway. In contrast to the situation of severe oxidative stress, most of proteins that are carbonylated in response to oxidant signaling do not undergo degradation. Our data suggest that proteins such as Rho GDI and peroxiredoxins undergo reversible protein carbonylation via enzyme-catalyzed decarbonylation. We propose that these reversible processes confer transient kinetics of cell signaling events. We also found that selected proteins such as annexin A1 are degraded after being carbonylated in response to ROS signaling. Annexin A1 was found to serve as a negative regulator of CBF/NF-Y and the annexin A1 degradation triggers the activation of this transcription factor. Thus, these two pathways which involve protein carbonylation can be activated during ROS signaling. (Supported by NIH)