Cid V J, Rodríguez-Escudero I, Andrés-Pons A, Romá-Mateo C, Gil A, den Hertog J, Molina M, Pulido R
Departamento de Microbiología II, Universidad Complutense de Madrid, Madrid, Spain.
Oncogene. 2008 Sep 18;27(41):5431-42. doi: 10.1038/onc.2008.240.
Model organisms have emerged as suitable and reliable biological tools to study the properties of proteins whose function is altered in human disease. In the case of the PI3K and PTEN human cancer-related proteins, several vertebrate and invertebrate models, including mouse, fly, worm and amoeba, have been exploited to obtain relevant functional information that has been conserved from these organisms to humans along evolution. The yeast Saccharomyces cerevisiae is an eukaryotic unicellular organism that lacks a canonical mammalian-like PI3K/PTEN pathway and PIP3 as a physiological second messenger, PIP2 being essential for its life. The mammalian PI3K/PTEN pathway can be reconstituted in S. cerevisiae, generating growth alteration phenotypes that can be easily monitored to perform in vivo functional analysis of the molecular constituents of this pathway. Here, we review the current nonmammalian model systems to study PTEN function, summarize our knowledge of PTEN orthologs in yeast species and propose the yeast S. cerevisiae as a sensitive biological sensor of PI3K oncogenicity and PTEN tumor suppressor activity.
模式生物已成为研究在人类疾病中功能发生改变的蛋白质特性的合适且可靠的生物学工具。就PI3K和PTEN这两种与人类癌症相关的蛋白质而言，已经利用了几种脊椎动物和无脊椎动物模型，包括小鼠、果蝇、蠕虫和变形虫，来获取在进化过程中从这些生物到人类都保守的相关功能信息。酿酒酵母是一种真核单细胞生物，它缺乏典型的类似哺乳动物的PI3K/PTEN途径以及作为生理第二信使的PIP3，PIP2对其生存至关重要。哺乳动物的PI3K/PTEN途径可以在酿酒酵母中重建，产生生长改变表型，这些表型可以很容易地被监测，以便对该途径的分子成分进行体内功能分析。在这里，我们综述了当前用于研究PTEN功能的非哺乳动物模型系统，总结了我们对酵母物种中PTEN直系同源物的认识，并提出酿酒酵母作为PI3K致癌性和PTEN肿瘤抑制活性的敏感生物传感器。
