Lu Zhimin, Hunter Tony
1] Brain Tumor Center and Department of Neuro-Oncology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA [2] Department of Molecular and Cellular Oncology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA [3] Cancer Biology Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA.
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Cell Res. 2014 Sep;24(9):1033-49. doi: 10.1038/cr.2014.109. Epub 2014 Aug 15.
Proline-directed phosphorylation is a posttranslational modification that is instrumental in regulating signaling from the plasma membrane to the nucleus, and its dysregulation contributes to cancer development. Protein interacting with never in mitosis A1 (Pin1), which is overexpressed in many types of cancer, isomerizes specific phosphorylated Ser/Thr-Pro bonds in many substrate proteins, including glycolytic enzyme, protein kinases, protein phosphatases, methyltransferase, lipid kinase, ubiquitin E3 ligase, DNA endonuclease, RNA polymerase, and transcription activators and regulators. This Pin1-mediated isomerization alters the structures and activities of these proteins, thereby regulating cell metabolism, cell mobility, cell cycle progression, cell proliferation, cell survival, apoptosis and tumor development.
脯氨酸定向磷酸化是一种翻译后修饰,在调节从质膜到细胞核的信号传导中起重要作用,其失调会促进癌症发展。与有丝分裂A1期蛋白相互作用的蛋白(Pin1)在多种癌症中过表达,它能使许多底物蛋白中特定的磷酸化丝氨酸/苏氨酸-脯氨酸键发生异构化,这些底物蛋白包括糖酵解酶、蛋白激酶、蛋白磷酸酶、甲基转移酶、脂质激酶、泛素E3连接酶、DNA内切酶、RNA聚合酶以及转录激活因子和调节因子。这种Pin1介导的异构化改变了这些蛋白的结构和活性,从而调节细胞代谢、细胞迁移、细胞周期进程、细胞增殖、细胞存活、凋亡以及肿瘤发展。