Posttranslational Regulation and Conformational Plasticity of PTEN
Posttranslational Regulation and Conformational Plasticity of PTEN
复制标题
磷酸酶与张力蛋白同源物（PTEN）的翻译后调控及构象可塑性
DOI：
10.1101/cshperspect.a036095
复制
发表时间：
2020-07-01
影响因子：
5.4
通讯作者：
Scott, Mark G. H.
中科院分区：
文献类型：
--
作者：
Kotelevets, Larissa;Trifault, Barbara;Scott, Mark G. H.
10号染色体上的磷酸酶和紧张素同源物缺失（PTEN）是一种在人类癌症中经常下调的肿瘤抑制因子。PTEN通过其脂质磷酸酶活性抑制磷脂酰肌醇3-磷酸激酶(PI3K)/AKT通路。PTEN的多种PI3K/ akt独立作用，蛋白磷酸酶活性和细胞核内的功能也被描述。因此，PTEN调控许多细胞过程，包括细胞增殖、存活、基因组完整性、极性、迁移和侵袭。即使PTEN功能剂量的适度减少也可能促进癌症的发展。因此，了解调节PTEN蛋白水平和功能的分子和细胞机制，以及这些机制在癌症背景下如何出错，是充分理解PTEN在肿瘤发生中的作用的关键。在这里，我们讨论了目前关于PTEN翻译后控制和构象可塑性的知识，以及在癌症中重建PTEN肿瘤抑制活性的治疗可能性。
Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor that is frequently down-modulated in human cancer. PTEN inhibits the phosphatidylinositol 3-phosphate kinase (PI3K)/AKT pathway through its lipid phosphatase activity. Multiple PI3K/AKT-independent actions of PTEN, protein-phosphatase activities and functions within the nucleus have also been described. PTEN, therefore, regulates many cellular processes including cell proliferation, survival, genomic integrity, polarity, migration, and invasion. Even a modest decrease in the functional dose of PTEN may promote cancer development. Understanding the molecular and cellular mechanisms that regulate PTEN protein levels and function, and how these may go awry in cancer contexts, is, therefore, key to fully understanding the role of PTEN in tumorigenesis. Here, we discuss current knowledge on posttranslational control and conformational plasticity of PTEN, as well as therapeutic possibilities toward reestablishment of PTEN tumor-suppressor activity in cancer.