engleski

NMEGP1 Gene/Protein from Capsaspora owcarzaki - Structure, Function AND Evolution

Nme (Nucleoside diphosphate kinases NDPK, Nm23) is an evolutionary conserved family of proteins present in all three domains of life. Their canonical role is the maintenance of the NTP pool in the cell by the phosphorylation of NDPs, although many other functions have been described. In vertebrates, Nme proteins are divided in two distinct groups. Group I has diversified after the appearance of vertebrates. Group II contains members that mostly have more ancient origins, with homologues present in unicellular eukaryotes. Ten Nme proteins have been identified in human: Nme1-4 belong to Group I, and Nme5-9 to Group II. Human Nme10, aka XRP2, has only a partial NDPK domain and does not belong to either group. Human Nme1 is the first know and the most studied metastasis suppressor. Decreased expression of Nme1 has been linked to metastatic phenotype of several tumor types. Due to a large research effort, we have a good knowledge of Nme1 properties in complex animals such as mammals. Nme seems to be involved in many biological processes such as metastasis, proliferation, development, differentiation, ciliary functions, vesicle transport and apoptosis in vertebrates. Biochemical mechanisms of these processes are still largely unknown. In our earlier study, we demonstrated that the earliest-branching simple animals – sponges (Porifera) possess a NmeGp1 homolog with similar biochemical properties as human Nme1/2. The work on Nme1/2 in unicellular eukaryotes has been so far very limited. No data are available on its properties in unicellular relatives of animals. Herein, we present the results of our research on NmeGp1 of Capsaspora owczarzaki, a member of Filasterea – a group of unicellular organisms closely related to animals. We show that the NmeGp1Co has properties strikingly similar to the sponge and human homologues. The protein did not change significantly during the transition to multicellularity and it has all the properties that make it a metastasis suppressor. This implies that metastasis suppression in mammals may be related to the intricate Nme1 pathways and interaction networks rather than a simple change of biochemical properties.

nm23/nme; evolution; Capsaspora Owczarzaky; protein structure; protein function

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