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Updated: Apr 21, 2026
Production, Crystallization, and Structure Determination of the IKK-binding Domain of NEMO
Published on: December 28, 2019
Janus-faces of NME-oncoprotein interactions
Nikolina Vlatković1, Shie-Hong Chang, Mark T Boyd
1p53/MDM2 Research Team, Cancer Research Centre, University of Liverpool, 200 London Road, Liverpool, L3 9TA, UK.
Abstract:
Since the identification of Nm23 (NME1, NME/NM23 nucleoside diphosphate kinase 1) as the first non-metastatic protein, a great deal of research on members of the NME family of proteins has focused on roles in processes implicated in carcinogenesis and particularly their regulation of cellular motility and the process of metastatic spread. To date, there are ten identified members of this family of genes, and these can be dichotomized into groups both taxonomically and by the presence or absence of their nucleoside diphosphate kinase activity with NMEs 1-4 encoding nucleoside diphosphate kinases (NDPKs) and NMEs 5-9 plus RP2 displaying little if any NDPK activity. NMEs are relatively small proteins that can form hetero-oligomers (typically hexamers), and given the apparent genetic redundancy of some NMEs and the number of different isoforms, it is perhaps not surprising that there remains a great deal of uncertainty regarding their function and even more regarding cellular mechanisms of action. Since residues that contribute to NDPK activity span much of the protein, it seems likely that the consequences of NME expression must be mediated through their NDPK activity, through interactions with other structures in cells including protein-protein interactions or through combinations of these. Our goal in this review is to focus on some of the protein-protein interactions that have been identified and to highlight some of the challenges that face this area of research.
Insights
The NME family of proteins, including Nm23 (NME1), are crucial in cancer progression and metastasis. Research highlights their roles in cellular motility and explores protein-protein interactions, despite functional uncertainties.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- The NME (non-metastatic) gene family, including Nm23 (NME1), has been extensively studied for its role in cancer progression and metastasis.
- NME family members are implicated in regulating cellular motility and metastatic spread.
- The NME family comprises ten identified genes, with NMEs 1-4 possessing nucleoside diphosphate kinase (NDPK) activity, while NMEs 5-9 and RP2 have little to no NDPK activity.
Purpose of the Study:
- To review identified protein-protein interactions within the NME family.
- To highlight the challenges in understanding NME protein functions and mechanisms of action.
- To explore how NME functions, potentially mediated by NDPK activity or protein interactions, contribute to cellular processes.
Main Methods:
- Literature review of NME family protein research.
- Analysis of studies investigating NME protein-protein interactions.
- Examination of research on NME family gene expression and NDPK activity.
Main Results:
- NME proteins can form hetero-oligomers, typically hexamers.
- Despite functional redundancy and isoforms, NME functions and mechanisms remain uncertain.
- NDPK activity and protein-protein interactions are proposed as key mediators of NME function.
Conclusions:
- Understanding NME protein-protein interactions is crucial for elucidating their roles in carcinogenesis and metastasis.
- Further research is needed to clarify the specific functions and mechanisms of action of different NME family members.
- The interplay between NDPK activity and protein interactions likely dictates NME's cellular impact.
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