Liu Tian, Wang Yiwei, Wang Yubing, Chan Andrew M
School of Biomedical Sciences, Room 705, Lo Kwee-Seong Integrated Biomedical Sciences Building, The Chinese University of Hong Kong, Hong Kong SAR, China.
School of Bioscience and Technology, Weifang Medical University, Weifang 261053, China.
Cancers (Basel). 2019 Aug 26;11(9):1247. doi: 10.3390/cancers11091247.
Phosphatase and tensin homolog deleted on chromosome 10 () is a tumor suppressor gene frequently found to be inactivated in over 30% of human cancers. encodes a 54-kDa lipid phosphatase that serves as a gatekeeper of the phosphoinositide 3-kinase pathway involved in the promotion of multiple pro-tumorigenic phenotypes. Although the PTEN protein plays a pivotal role in carcinogenesis, cumulative evidence has implicated it as a key signaling molecule in several other diseases as well, such as diabetes, Alzheimer's disease, and autism spectrum disorders. This finding suggests that diverse cell types, especially differentiated cells, express PTEN. At the cellular level, PTEN is widely distributed in all subcellular compartments and organelles. Surprisingly, the cytoplasmic compartment, not the plasma membrane, is the predominant subcellular location of PTEN. More recently, the finding of a secreted 'long' isoform of PTEN and the presence of PTEN in the cell nucleus further revealed unexpected biological functions of this multifaceted molecule. At the regulatory level, PTEN activity, stability, and subcellular distribution are modulated by a fascinating array of post-translational modification events, including phosphorylation, ubiquitination, and sumoylation. Dysregulation of these regulatory mechanisms has been observed in various human diseases. In this review, we provide an up-to-date overview of the knowledge gained in the last decade on how different functional domains of PTEN regulate its biological functions, with special emphasis on its subcellular distribution. This review also highlights the findings of published studies that have reported how mutational alterations in specific PTEN domains can lead to pathogenesis in humans.
第10号染色体缺失的磷酸酶和张力蛋白同源物（PTEN）是一种肿瘤抑制基因，在超过30%的人类癌症中经常被发现失活。PTEN编码一种54 kDa的脂质磷酸酶，它是磷酸肌醇3激酶途径的守门人，该途径参与多种促肿瘤表型的促进。尽管PTEN蛋白在致癌过程中起关键作用，但越来越多的证据表明它也是其他几种疾病中的关键信号分子，如糖尿病、阿尔茨海默病和自闭症谱系障碍。这一发现表明多种细胞类型，尤其是分化细胞，表达PTEN。在细胞水平上，PTEN广泛分布于所有亚细胞区室和细胞器中。令人惊讶的是，PTEN在细胞质区室而非质膜中是主要的亚细胞定位。最近，PTEN分泌型“长”异构体的发现以及PTEN在细胞核中的存在进一步揭示了这种多面分子意想不到的生物学功能。在调控水平上，PTEN的活性、稳定性和亚细胞分布受到一系列迷人的翻译后修饰事件的调节，包括磷酸化、泛素化和类泛素化。在各种人类疾病中都观察到了这些调控机制的失调。在这篇综述中，我们提供了过去十年中关于PTEN不同功能域如何调节其生物学功能所获得知识的最新概述，特别强调了其亚细胞分布。这篇综述还突出了已发表研究的发现，这些研究报道了PTEN特定结构域的突变改变如何导致人类发病机制。
