Nucleoside diphosphate kinase (NDPK, NM23, AWD): recent regulatory advances in endocytosis, metastasis, psoriasis, insulin release, fetal erythroid lineage and heart failure; translational medicine exemplified.
The guest editor (AM) provides his perspective on the most recent advances on nucleoside diphosphate kinase (NDPK, otherwise known as AWD or NM23) showcasing phospho-histidine biochemistry and its impact on diverse pathology when disordered. His co-author (SO) provides state-of-the-art analyses from the European institute of Bioinformatics in an appendix to support the most recent advances made by the NDPK community. Unfortunately, to those outside the field, NDPK is often dismissed as a tiny 'ancient housekeeper' protein found in marine sponges, social amoebae, worms, fruit flies, rodents and humans but the state-of-the-art papers overviewed here show that NDPK does not act simply in mindless rote, inter-converting cellular 'energy currencies'. That two NDPK isoforms regulate fetal erythroid lineage is a developmental case in point. Seminal Cancer Research UK support is gratefully acknowledged that generated additional resources to enable the NDPK community to meet in Dundee in 2007 ( www.dundee.ac.uk/mchs/ndpk ; next meeting is planned: 2010/Mannheim-Heidelberg). The presented papers illustrate the point that when scientists are left alone 'shut up in the narrow cell of their laboratory' (as the philosopher Ortega once said, a sentiment echoed by Erwin Schrödinger), then progress will ultimately occur bridging the gap between specialization and translation for human benefit. To aid translation, this overview initially introduces the NDPK family to the non-specialist, who serendipitously finds these proteins in their biology. This is immediately followed by examples of the diverse biology generated by this self-aggregating group of multi-functional proteins and finally capped by an emerging idea explaining how this diversity might arise.
Division of Medical Sciences, Tayside Institute of Child Health, Ninewells Hospital Medical School, Dundee DD19SY, Scotland, UK. a.mehta@dundee.ac.uk
Anil
A
Mehta
Sandra
S
Orchard
D019070:Cell Lineage / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics*; D004912:Erythrocytes / Q000166:cytology / Q000201:enzymology*; D005333:Fetus / Q000378:metabolism; D006333:Heart Failure / Q000235:genetics; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism*; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D009701:Nucleoside-Diphosphate Kinase / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D007527:Isoenzymes; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase