Laboratory of Molecular Genetics, Division of Molecular Biology, Ruđer Bošković Institute, Zagreb, Croatia.
Laboratory of Molecular Oncology, Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
Lab Invest. 2018 Mar;98(3):304-314. doi: 10.1038/labinvest.2017.134. Epub 2018 Feb 5.
Nucleoside diphosphate kinases are enzymes present in all domains of life. In animals, they are called Nme or Nm23 proteins, and are divided into group I and II. Human Nme1 was the first protein identified as a metastasis suppressor. Because of its medical importance, it has been extensively studied. In spite of the large research effort, the exact mechanism of metastasis suppression remains unclear. It is unknown which of the biochemical properties or biological functions are responsible for the antimetastatic role of the mammalian Nme1. Furthermore, it is not clear at which point in the evolution of life group I Nme proteins acquired the potential to suppress metastasis, a process that is usually associated with complex animals. In this study we performed a series of tests and assays on a group I Nme protein from filasterean Capsaspora owczarzaki, a close unicellular relative of animals. The aim was to compare the protein to the well-known human Nme1 and Nme2 homologs, as well as with the homolog from a simple animal-sponge (Porifera), in order to see how the proteins changed with the transition to multicellularity, and subsequently in the evolution of complex animals. We found that premetazoan-type protein is highly similar to the homologs from sponge and human, in terms of biochemical characteristics and potential biological functions. Like the human Nme1 and Nme2, it is able to diminish the migratory potential of human cancer cells in culture.
核苷二磷酸激酶存在于所有生命领域。在动物中，它们被称为 Nme 或 Nm23 蛋白，并分为 I 组和 II 组。人类 Nme1 是第一个被确定为转移抑制因子的蛋白质。由于其医学重要性，它已经被广泛研究。尽管进行了大量的研究，但转移抑制的确切机制仍不清楚。目前尚不清楚哪种生化特性或生物学功能负责哺乳动物 Nme1 的抗转移作用。此外，也不清楚在生命进化的哪个阶段，I 组 Nme 蛋白获得了抑制转移的潜力，而转移通常与复杂的动物有关。在这项研究中，我们对来自 Filasterean Capsaspora owczarzaki 的 I 组 Nme 蛋白进行了一系列测试和分析，Capsaspora owczarzaki 是动物的一种密切的单细胞近亲。目的是将该蛋白与著名的人类 Nme1 和 Nme2 同源物以及来自简单动物海绵（多孔动物门）的同源物进行比较，以了解蛋白质在向多细胞生物的转变过程中以及在复杂动物的进化过程中发生了哪些变化。我们发现，前后生动物型蛋白在生化特征和潜在生物学功能方面与海绵和人类的同源物非常相似。与人类 Nme1 和 Nme2 一样，它能够减少人类癌细胞在培养中的迁移潜力。
