Sumoylation-deficient Prdx6 gains protective function by amplifying enzymatic activity and stability and escapes oxidative stress-induced aberrant Sumoylation.

摘要: Aberrant Sumoylation of protein(s) in response to oxidative stress or during aging is known be involved etiopathogenesis many diseases. Upon stress, Peroxiredoxin (Prdx) 6 aberrantly Sumoylated by Sumo1, resulting loss functions and cell death. We identified lysines (K) 122 142 as the major Sumo1 conjugation sites Prdx6. Intriguingly, mutant Prdx6 K122/142 R (arginine) gained protective efficacy, increasing abundance promoting glutathione (GSH) peroxidase acidic calcium-independent phospholipase A2 (aiPLA2) activities. Using lens epithelial cells derived from targeted inactivation Prdx6−/− gene relative enzymatic stability assays, we discovered dramatic increases GSH-peroxidase (30%) aiPLA2 (37%) activities mutant, suggesting destabilized integrity. Prdx6−/−LECs with EGFP-Sumo1 transduced co-expressed TAT-HA-Prdx6K122/142 R pGFP-Prdx6K122/142 R were highly resistant demonstrating protein escaped interrupted aberrant Sumoylation-mediated death pathway. Mutational analysis functional showed that both PLA2 active necessary for function, phosphorylation (at T177 residue) was essential optimum activity. Our work reveals involvement stress-induced dysregulation function. Mutant at its escapes abates this adverse process maintaining integrity gaining propose K122/142R form a TAT-fusion may an easily applicable intervention pathobiology related signaling stress.