SUPEROXIDE-INDUCIBLE PROTEIN A170 AND REDOX REGULATION

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We have been characterizing cDNA clones that encode novel oxidative stress-inducible proteins from mouse macrophages. We have found a novel protein termed A170 that has a Zn-finger motif, a PEST-sequence and several potential phosphorylation sites for protein kinases. The structural features suggest that it may work as a metabolic regulator rather than as an antioxidant itself. The A170 protein can be induced in the macrophages by low doses of oxidative stress agents such as paraquat and diethyl maleate. In the murine macrophages, we have found protein kinases that phosphorylate A170 protein in vitro. Using specific protease inhibitors, we have suggested that A170 protein is rapidly degraded by proteasome. We also have shown that micromolar concentrations of hydrogen peroxide induced the level of A170 protein without significant increase in the level of A170 mRNA.This result suggests a possibility that oxidative stress may retard the degradation of A170 protein in the cells. Interestingly, recent reports by US research groups show that a human protein, 90% identical to A170, has been cloned either as an ligand to SH2 domain of tyrosine kinase LCK or to a novel cytokine receptor induced upon infection by EB-virus. These results suggest that the A170 protein plays a role in the intracellular signal transduction under oxidative stress.