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Regulation of PRDX1 peroxidase activity by Pin1

机译：Pin1对PRDX1过氧化物酶活性的调节

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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.
机译：Pin1异构化磷酸化的Ser / Thr-Pro肽键，并通过诱导构象变化来调节其结合蛋白的功能。已根据Pin1敲除小鼠的表型及其与寿命调节蛋白p66Shc的相互作用，提出了Pin1在衰老过程中的参与。在这项研究中，我们利用蛋白质组学方法，并确定了另一种衰老调节剂过氧化物酶1（PR DX1）作为一种新型的Pin1结合蛋白。 Pin1通过与PR DX1的磷酸-Thr90-Pro91基序相互作用而与PR DX1结合，并且当PR DX1的Thr90发生突变时，这种相互作用就消失了。 Pin1结合基序Thr-Pro在2-Cys PR DX，PR DX1-4中是保守的，并且还显示了Pin1和PR DX2-4之间的相互作用。在Pin1-/-小鼠胚胎成纤维细胞（MEF s）中观察到2-Cys PR DXs的过氧化氢积累增加和过氧化物酶活性降低，当Pin1重新引入细胞后PR DXs的活性得以恢复。 。 PR DX1在Thr90处的磷酸化已显示可抑制其过氧化物酶活性。然而，如何精确地调节PR DX1的活性仍不清楚。在这里，我们证明Pin1促进了蛋白磷酸酶2A介导的PR DX1的去磷酸化，这有助于解释PR DX1的非活性磷酸化形式在Pin1-/-MEF中的积累。总的来说，我们确定Pin1为新型PR DX1结合蛋白，并提出Pin1调节细胞中活性氧代谢的机制。

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