Institute of Pathology, Charité - Universitätsmedizin Berlin, 10117, Berlin, Germany.
Integrative Research Institute Life Sciences, Humboldt Universität Berlin, 10115, Berlin, Germany.
Cell Commun Signal. 2018 Aug 15;16(1):46. doi: 10.1186/s12964-018-0256-8.
Proteins of the ubiquitously expressed core proteome are quantitatively correlated across multiple eukaryotic species. In addition, it was found that many protein paralogues exhibit expression anticorrelation, suggesting that the total level of protein with a given functionality must be kept constant.
We performed Spearman's rank correlation analyses of gene expression levels for the RAS GTPase subfamily and their regulatory GEF and GAP proteins across tissues and across individuals for each tissue. A large set of published data for normal tissues from a wide range of species, human cancer tissues and human cell lines was analysed.
We show that although the multidomain regulatory proteins of Ras GTPases exhibit considerable tissue and individual gene expression variability, their total amounts are balanced in normal tissues. In a given tissue, the sum of activating (GEFs) and deactivating (GAPs) domains of Ras GTPases can vary considerably, but each person has balanced GEF and GAP levels. This balance is impaired in cell lines and in cancer tissues for some individuals.
Our results are relevant for critical considerations of knock out experiments, where functionally related homologs may compensate for the down regulation of a protein.
普遍表达的核心蛋白质组的蛋白质在多种真核生物物种中具有定量相关性。此外，还发现许多蛋白质同工型表现出表达反相关，这表明具有给定功能的蛋白质的总水平必须保持恒定。
我们对 RAS GTPase 亚家族及其在组织和个体中的调节 GEF 和 GAP 蛋白的基因表达水平进行了 Spearman 等级相关分析。对来自广泛物种的正常组织、人类癌症组织和人类细胞系的大量已发表数据进行了分析。
我们表明，尽管 Ras GTPase 的多结构域调节蛋白表现出相当大的组织和个体基因表达可变性，但它们的总量在正常组织中是平衡的。在给定的组织中，Ras GTPase 的激活（GEFs）和失活（GAPs）结构域的总和变化很大，但每个人的 GEF 和 GAP 水平都是平衡的。在某些个体的细胞系和癌症组织中，这种平衡受到了损害。
我们的研究结果与敲除实验的重要考虑因素有关，在这些实验中，功能相关的同源物可能会补偿蛋白质的下调。
