The Antioxidant Enzyme Methionine Sulfoxide Reductase A (MsrA) Interacts with Jab1/CSN5 and Regulates Its Function

Antioxidants

Zachary Adams¹  Julie Maupin-Furlow¹  Honglian Shi²  Jackob Moskovitz²  Beichen Jiang²  Shannon Moonah³ 

[1] Department of Microbiology and Cell Science, College of Agricultural and Life Sciences, University of Florida, Gainesville, FL 32611, USA;Department of Pharmacology and Toxicology, School of Pharmacy, University of Kansas, Lawrence, KS 66045, USA;Division of Infectious Diseases, University of Virginia, 345 Crispell Drive, MR-6, Room 2715, Charlottesville, VA 22908, USA;

关键词: methionine oxidation;    posttranslational modification;    neddylation;    ubiquitin;    brain;    oxidative stress;   

DOI  :  10.3390/antiox9050452

来源: DOAJ

【 摘 要 】

Methionine sulfoxide (MetO) is an oxidative posttranslational modification that primarily occurs under oxidative stress conditions, leading to alteration of protein structure and function. This modification is regulated by MetO reduction through the evolutionarily conserved methionine sulfoxide reductase (Msr) system. The Msr type A enzyme (MsrA) plays an important role as a cellular antioxidant and promotes cell survival. The ubiquitin- (Ub) like neddylation pathway, which is controlled by the c-Jun activation domain-binding protein-1 (Jab1), also affects cell survival. Jab1 negatively regulates expression of the cell cycle inhibitor cyclin-dependent kinase inhibitor 1B (P27) through binding and targeting P27 for ubiquitination and degradation. Here we report the finding that MsrA interacts with Jab1 and enhances Jab1′s deneddylase activity (removal of Nedd8). In turn, an increase is observed in the level of deneddylated Cullin-1 (Cul-1, a component of E3 Ub ligase complexes). Furthermore, the action of MsrA increases the binding affinity of Jab1 to P27, while MsrA ablation causes a dramatic increase in P27 expression. Thus, an interaction between MsrA and Jab1 is proposed to have a positive effect on the function of Jab1 and to serve as a means to regulate cellular resistance to oxidative stress and to enhance cell survival.

【 授权许可】

Unknown