Department of Biochemistry, Department of Biomedical Sciences, Research Center for Aging and Geriatrics, Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju, 501-190, Republic of Korea.
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, 120-750, Republic of Korea.
Redox Biol. 2020 Jul;34:101553. doi: 10.1016/j.redox.2020.101553. Epub 2020 May 3.
Phosphatase and tensin homologs deleted on chromosome 10 (PTEN) is a potent tumor suppressor and often dysregulated in cancers. Cellular PTEN activity is restrained by the oxidation of active-site cysteine by reactive oxygen species (ROS). Recovery of its enzymatic activity predominantly depends on the availability of cellular thioredoxin (Trx) and peroxiredoxins (Prx), both are important players in cell signaling. Trx and Prx undergo redox-dependent conformational changes through the oxidation of cysteine residues at their active sites. Their dynamics are essential for protein functionality and regulation. In this review, we summarized the recent advances regarding the redox regulation of PTEN, with a specific focus on our current state-of-the-art understanding of the redox regulation of PTEN. We also proposed a tight association of the redox regulation of PTEN with Trx dimerization and Prx hyperoxidation, providing guidance for the identification of novel therapeutic targets.
第 10 号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）是一种有效的肿瘤抑制因子，在癌症中经常失调。细胞 PTEN 活性受到活性位点半胱氨酸被活性氧（ROS）氧化的限制。其酶活性的恢复主要取决于细胞硫氧还蛋白（Trx）和过氧化物酶（Prx）的可用性，两者都是细胞信号转导中的重要参与者。Trx 和 Prx 通过其活性位点半胱氨酸残基的氧化发生氧化依赖性构象变化。它们的动力学对于蛋白质功能和调节至关重要。在这篇综述中，我们总结了关于 PTEN 氧化还原调节的最新进展，特别关注我们目前对 PTEN 氧化还原调节的最新认识。我们还提出了 PTEN 的氧化还原调节与 Trx 二聚化和 Prx 超氧化之间的紧密联系，为鉴定新的治疗靶点提供了指导。
