engleski

Can the sponge NM23-SD1 replace the human homolog in its antimetastatic activity?

Nucleoside diphosphate kinases Nm23/NDPK are evolutionary conserved enzymes present in Bacteria, Archaea and Eukarya, with human Nm23-H1 as the most studied representative of the family and the first identifed metastasis suppressor. Here we report new results on the metastasis suppressor gene/protein homolog from marine sponge Suberites domuncula, Nm23-SD1. The goal of this study was to reveal the biochemical characteristics of the sponge Nm23-SD1 gene/protein and determine if the sponge homolog can replace the proposed antimetastatic function of Nm23-H1 in cancer cells. Furthermore, we have determined the structure of the nm23-SD1 gene and compared it with the metazoan homologues. In our study we have discovered that the sponge Nm23-SD1 protein has a similar level of kinase activity as its human homolog, does not cleave negatively supercoiled DNA and shows nonspecific DNA-binding activity. The sponge Nm23-SD1 forms a hexamer, same as the human homolog Nm23-H1, and all other eukaryotic Nm23 proteins. Nm23-SD1 occupies the same subcellular localization in human cells as the human Nm23-H1. Stable clones expressing sponge Nm23-SD1 inhibited the migratory potential of CAL 27 cells, as already reported for Nm23-H1, which suggests that its function in migration processes was engaged long before the composition of true tissues, and genesis of tumors and metastasis. This study suggests that the ancestor of all Metazoa already possessed a functional Nm23 metastatic suppressor gene/protein homolog and that several of its multiple functions existed before the emergence of true multicellularity.

nm23-SD1; nm23-H1; NDPK; metastasis supression; sponge

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