%0 Journal Article
%T Sponge non-metastatic Group I Nme gene/protein - structure and function is conserved from sponges to humans
%A Drago Perina
%A Maja Bosnar
%A Ru£¿ica Bago
%A Andreja Miko£¿
%A Matija Harcet
%A Martina De£¿eljin
%A Helena £¿etkovi£¿
%J BMC Evolutionary Biology
%D 2011
%I BioMed Central
%R 10.1186/1471-2148-11-87
%X We found that sponge genes coding for Group I Nme protein are intron-rich. Furthermore, we discovered that the sponge NmeGp1Sd protein has a similar level of kinase activity as its human homolog Nme1, does not cleave negatively supercoiled DNA and shows nonspecific DNA-binding activity. The sponge NmeGp1Sd forms a hexamer, like human Nme1, and all other eukaryotic Nme proteins. NmeGp1Sd interacts with human Nme1 in human cells and exhibits the same subcellular localization. Stable clones expressing sponge NmeGp1Sd inhibited the migratory potential of CAL 27 cells, as already reported for human Nme1, which suggests that Nme's function in migratory processes was engaged long before the composition of true tissues.This study suggests that the ancestor of all animals possessed a NmeGp1 protein with properties and functions similar to evolutionarily recent versions of the protein, even before the appearance of true tissues and the origin of tumors and metastasis.The Nme family, initially called nucleoside diphosphate kinases (NDPK) or Nm23, are evolutionarily conserved proteins present in all three domains of life: Bacteria, Archaea and Eukarya [1]. Vertebrate Nme enzymes can be separated into two evolutionarily distinct groups. In humans, Group I includes Nme1-Nme4 and Group II includes Nme5-Nme9 proteins. Nme10, also known as XRP2, was the last described member and apparently has a somewhat different evolutionary history to Group I or Group II genes; it is characterized by a recent insertion of a partial NDPK domain [2]. The human Nme1 was recognized as the first metastasis suppressor and is the most studied member of the Nme family of proteins [3]. In contrast to tumor suppressor genes, metastasis suppressor genes do not abolish or diminish the tumorigenicity of a tumor, they only affect its potential to metastasise. This means that a metastasis suppressor fulfills its biological function within the processes linked to the metastatic cascade: tumor cell dissociation,
%U http://www.biomedcentral.com/1471-2148/11/87