engleski

Nme family members in non-bilaterian Metazoans

Our studies are focused on the characterization of strucutre and function of nme homologs/orthologs in 'non-bilaterian' Metazoa, namely sponges (Porifera). Sponges are simple animals and are considered to be the closest to the common metazoan ancestor. In our studies we have found that the sponge NmGp1Sd 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 NmGp1Sd forms a hexamer, same as the human Nme1/2, and displays the same subcellular localization in human cells as the human Nme1. Stable clones expressing NmGp1Sd inhibited the migratory potential of CAL 27 cells, as already reported for Nme1, which suggests that its function in migration processes was engaged before the origin of true tissues, and genesis of tumors and metastasis. This suggests that the common ancestor of Metazoa possessed a functional Nm23Gp1 metastatic suppressor gene/protein homolog and that several of its multiple functions existed before the emergence of true multicellularity. In contrast, our findings on the sponge version of Nme6, suggest that this family member changed substantially during evolution and that complex actions of Nme6 in different biological processes probably correlate with increasing complexity of the organism. Nme6Sd, does not possess NDPK activity and does not localize in mitochondria as the human nme6, although it has a mitochondrial signalling sequence. It lacks two recent introns that comprise miRNAs in humans, and has different transcriptional binding sites in the promoter region. Our current studies are focused on further characterization of the sponge and human nme6, as well as on the nmeGp1 of a unicellular metazoan relative Capsospora owczarzaki .

nme 1; nme 6; metazoa; evolution

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