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|Title:||Regulation of PRDX1 peroxidase activity by Pin1|
|Keywords:||Aging and reactive oxygen species|
|Citation:||Chu, K.L., Lew, Q.J., Rajasegaran, V., Kung, J.T., Zheng, L., Yang, Q., Shaw, R., Cheong, N., Liou, Y.-C., Chao, S.-H. (2013-03-15). Regulation of PRDX1 peroxidase activity by Pin1. Cell Cycle 12 (6) : 944-952. ScholarBank@NUS Repository. https://doi.org/10.4161/cc.23916|
|Abstract:||Pin1 isomerizes the phosphorylated Ser/Thr-Pro peptide bonds and regulates the functions of its binding proteins by inducing conformational changes. Involvement of Pin1 in the aging process has been suggested based on the phenotype of Pin1-knockout mice and its interaction with lifespan regulator protein, p66Shc. In this study, we utilize a proteomic approach and identify peroxiredoxin 1 (PR DX1), another regulator of aging, as a novel Pin1 binding protein. Pin1 binds to PR DX1 through interacting with the phospho-Thr90-Pro91 motif of PR DX1, and this interaction is abolished when the Thr90 of PR DX1 is mutated. The Pin1 binding motif, Thr-Pro, is conserved in the 2-Cys PR DXs, PR DX1-4 and the interactions between Pin1 and PR DX2-4 are also demonstrated. An increase in hydrogen peroxide buildup and a decrease in the peroxidase activity of 2-Cys PR DXs were observed in Pin1-/- mouse embryonic fibroblasts (MEF s), with the activity of PR DXs restored when Pin1 was re-introduced into the cells. Phosphorylation of PR DX1 at Thr90 has been shown to inhibit its peroxidase activity; however, how exactly the activity of PR DX1 is regulated by phosphorylation still remains unknown. Here, we demonstrate that Pin1 facilitates the protein phosphatase 2A-mediated dephosphorylation of PR DX1, which helps to explain the accumulation of the inactive phosphorylated form of PR DX1 in Pin1-/- MEF s. Collectively, we identify Pin1 as a novel PR DX1 binding protein and propose a mechanism for Pin1 in regulating the metabolism of reactive oxygen species in cells. © 2013 Landes Bioscience.|
|Source Title:||Cell Cycle|
|Appears in Collections:||Staff Publications|
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