@article{APS10357,
author = {Li Jiang and Xiao-bing Chen and Qian Wu and Hai-ying Zhu and Cheng-yong Du and Mei-dan Ying and Qiao-jun He and Hong Zhu and Bo Yang and Ji Cao},
title = {The C terminus of DJ-1 determines its homodimerization, MGO detoxification activity and suppression of ferroptosis},
journal = {Acta Pharmacologica Sinica},
volume = {42},
number = {7},
year = {2021},
keywords = {},
abstract = {DJ-1 is a multifunctional protein associated with cancers and autosomal early-onset Parkinson disease. Besides the well- documented antioxidative stress activity, recent studies show that DJ-1 has deglycation enzymatic activity and anti-ferroptosis effect. It has been shown that DJ-1 forms the homodimerization, which dictates its antioxidative stress activity. In this study, we investigated the relationship between the dimeric structure of DJ-1 and its newly reported activities. In HEK293T cells with Flag- tagged and Myc-tagged DJ-1 overexpression, we performed deletion mutations and point mutations, narrowed down the most critical motif at the C terminus. We found that the deletion mutation of the last three amino acids at the C terminus of DJ-1 (DJ-1 ΔC3) disrupted its homodimerization with the hydrophobic L187 residue being of great importance for DJ-1 homodimerization. In addition, the ability in methylglyoxal (MGO) detoxification and deglycation was almost abolished in the mutation of DJ-1 ΔC3 and point mutant L187E compared with wild-type DJ-1 (DJ-1 WT). We also showed the suppression of erastin-triggered ferroptosis in DJ-1−/− mouse embryonic fibroblast cells was abolished by ΔC3 and L187E, but partially diminished by V51C. Thus, our results demonstrate that the C terminus of DJ-1 is crucial for its homodimerization, deglycation activity, and suppression of ferroptosis.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10357}
}