engleski

The metastasis suppressor gene family Nme/Nm23/NDPK- lessons from model organisms

The Nme gene/protein family, initially called nucleoside diphosphate kinase (Nm23/NDPK), consists of evolutionarily conserved genes/proteins present in all three domains of life. This family of proteins was originally named after the first member identified, Nm23- H1/Nme1, which is responsible for metastasis suppression of many tumor types. The Nme1/NDPKA and Nme2/NDPKB are two units of a well-known enzyme nucleoside-diphosphate kinase (NDPK), which transfers the terminal phosphate form (d)NTPs to (d)NDPs and is, therefore, responsible for the maintenance of the cellular nucleotide pool. Besides this housekeeping role, the Nme/NDPK proteins have been assigned several additional biochemical functions. Numerous proteins from evolutionary distinct organisms exhibit extraordinary similarity in their structures with their orthologs in mammals including humans. Therefore, it is presumed that they have similar or identical biochemical and biological functions. The goal of our studies was to determine the structure, function and evolution of several members of the Nme/NDPK family in model systems evolutionary very distinct form humans. Our studies were focused on 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. Series of biochemical and biological tests, especially the formation of stable clones expressing the sponge variant of the Group I Nme gene which inhibited the migratory potential of human tumor cells, implied 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 NmeGp1 metastatic suppressor gene/protein homolog and that several of its multiple functions existed before the emergence of true multicellularity. Recently we have done a similar study on the Nme homolog from a unicellular filasterean organism Capsaspora owczarzaki, which was also able to suppress migration potential of human cells although the human, sponge and filasterean proteins exhibit some structural differences.

NME ; Nm23 ; model organisms ; metastasis suppressors

nije evidentirano