Characterization of Nme5-Like Gene/Protein from the Red Alga Chondrus Crispus

Abstract

The Nme gene/protein family of nucleoside diphosphate kinases (NDPK) was originally named after its member Nm23-H1/Nme1, the first identified metastasis suppressor. Human Nme proteins are divided in two groups. They all possess nucleoside diphosphate kinase domain (NDK). Group I (Nme1-Nme4) display a single type NDK domain, whereas Group II (Nme5-Nme9) display a single or several different NDK domains, associated or not associated with extra-domains. Data strongly suggest that, unlike Group I, none of the members of Group II display measurable NDPK activity, although some of them autophosphorylate. The multimeric form is required for the NDPK activity. Group I proteins are known to multimerize, while there are no data on the multimerization of Group II proteins. The Group II ancestral type protein was shown to be conserved in several species from three eukaryotic supergroups. Here, we analysed the Nme protein from an early branching eukaryotic lineage, the red alga Chondrus crispus. We show that the ancestral type protein, unlike its human homologue, was fully functional multimeric NDPK with high affinity to various types of DNA and dispersed localization throughout the eukaryotic cell. Its overexpression inhibits both cell proliferation and the anchorage-independent growth of cells in soft agar but fails to deregulate cell apoptosis. We conclude that the ancestral gene has changed during eukaryotic evolution, possibly in correlation with the protein function.

NME6 is a phosphotransfer-inactive, monomeric NME/NDPK family member and functions in complexes at the interface of mitochondrial inner membrane and matrix

“…In contrast to Group I, research on Group II proteins (NME5-NME9) has been scarce. It seems that the Group II members emerged very early in the eukaryotic evolution [ 32 ]. Group II NME members are more divergent among themselves (28–45% amino acid identity) and dissimilar to Group I proteins (25–34% amino acid identity) [ 4 , 33 ].…”

“…NME6 probably arose by duplication of a NME5-like gene with the emergence of Amoebozoa, such as Dyctiostelium [ 32 ]. As compared to other NME family members, especially NME1 and NME2, very few studies addressed NME6, although its first description by two separate groups dates back over 20 years.…”

Emerging Molecular Connections between NM23 Proteins, Telomeres and Telomere-Associated Factors: Implications in Cancer Metastasis and Ageing

“…The NM23-H2 homologue in zebrafish Danio rerio known as “NM23-B”, discovered based on 87.3% sequence similarity, was also found to interact with the telomeric DNA sequence (TTAGGG) 6 [ 7 ]. Additionally, a close homologue of human NM23-H5 (NME5) recently found in the red alga Chondrus crispus —and therefore named NME5-likeCc—was also found to interact with telomeric DNA (TTAGGG) 6 in vitro [ 8 ].…”

The Complex Functions of the NME Family—A Matter of Location and Molecular Activity

“…Further studies on rat models of metabolic syndrome or heterozygous NME7 knock-out suggest a link between NME7 and glucose intolerance or adiposity [ 51 , 52 ]. NME7 in the red algae Chondrus crispus , an early eukaryote, differs from its human homologue in its oligomeric structure and possibly in function [ 53 ]. Finally, a most recent study identifies NME7 as an activator of Wnt/β-catenin signaling in hepatocellular carcinoma, based on a hitherto unknown serine protein kinase activity of NME7 [ 54 ].…”