Characterization of a group I Nme protein of Capsaspora owczarzaki-a close unicellular relative of animals

Ćetković, Helena; Bosnar Herak, Maja; Perina, Dragutin; Mikoč, Andreja; Deželjin, Martina; Belužić, Robert; Bilandžija, Helena; Ruiz-Trillo, Iñaki; Harcet, Matija (2018) Characterization of a group I Nme protein of Capsaspora owczarzaki-a close unicellular relative of animals. Laboratory Investigation, 98 (3). pp. 304-314. ISSN 0023-6837

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Official URL: https://www.nature.com/articles/labinvest2017134

Abstract

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.

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Article

Additional Information:

We are grateful to Arnau Sebe-Pedros for his help in analyzing and interpreting the RNAseq data and to Petar Ozretic for helping us with statistical analysis of the migration assays. This work was funded by Croatian MSES grants 098-0982913-2478 to HC and 098-09824642513 to MHB, and the Croatian Science Foundation project IP-2016-06-4021 to MHB. MH received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007-2013/ under REA grant agreement no. 330925. IR-T is supported by a grant from Ministerio de Economia y Competitividad (MINECO) (BFU2014-57779-P) and a European Research Council Consolidator Grant (ERC2012Co616960) to IR-T, the former co-funded by the European Regional Development Fund. We acknowledge support from Secretaria d'Universitats i Recerca de la Generalitat de Catalunya (Project 2014 SGR 619).

Uncontrolled Keywords:

Metastasis suppressor; Nme1; Nm23; Capsaspora owczarzaki; evolution

Subjects:

NATURAL SCIENCES
NATURAL SCIENCES > Biology > Biochemistry and Molecular Biology

Divisions:

Division of Molecular Biology

Projects: