NME1

Fig1. Schematic representation of four common functions of Nm23-H1. (Saurabh Pandey, 2018)

What is NME1 protein?

NME1 (NME/NM23 nucleoside diphosphate kinase 1) gene is a protein coding gene which situated on the long arm of chromosome 17 at locus 17q21. NME1, full name NME/NM23 nucleoside diphosphokinase 1 (NME1), is a multifunctional enzyme that plays an important role in inhibiting tumor cell invasion and metastasis. This protein is evolutionarily conserved and plays a role in a variety of biological processes, including cell proliferation, differentiation, development, signal transduction, endocytosis of G protein-coupled receptors, and gene expression. Expression levels of NME1 are reduced in highly metastasized cells, where it exists as A hexamer composed of subunits A (encoded by the NME1 gene) and B (encoded by the NME2 gene). NME1 protein shows cytoplasmic expression in a variety of tissues and has low tissue specificity in most tissues. The NME1 protein is consisted of 152 amino acids and its molecular mass is approximately 17.1 kDa.

What is the function of NME1 protein?

One of the main functions of NME1 is as a nucleoside diphosphokinase (NDPK), which is involved in the interconversion between the cell kernel side diphosphate (NDP) and triphosphate (NTP) by transferring the α-phosphate group. This activity is essential for maintaining the balance of ATP and other key nucleotides within the cell. By influencing the level and distribution of ATP in cells, NME1 is involved in the regulation of cytoskeleton rearrangement and cell motility, which has important significance for cell migration and invasion ability. NME1 plays a role in the endocytosis of G protein-coupled receptors, which involves the uptake of substances mediated by receptors on the cell surface. In addition, NME1 plays a role in cells responding to oxidative and metabolic stress.

NME1 Related Signaling Pathway

NME1 (also known as nm23-H1) is a widely expressed, multifunctional protein that plays a key role in many biological processes. NME1 is mainly involved in a variety of signaling pathways as a nucleoside diphosphate kinase (NDPK), and its core function is to catalyze the conversion of nucleoside diphosphate (NDPs) to the corresponding triphosphate (NTPs), so as to maintain the balance of intracellular nucleotide pools. NME1 is able to influence cell proliferation and survival by regulating the activity of the Raf-MEK-ERK pathway, which is an important signal transduction pathway in many types of cancer. NME1 interacts with the PI3K/Akt pathway, which plays a key role in cell survival, growth, and metabolism.

NME1 Related Diseases

Mutations in the NME1 gene have been identified in neuroblastoma, which originates from neural crest cells and is one of the most common solid tumors in children. Low expression of the NME1 gene has been associated with advanced metastasis of a variety of epithelial cancers, including melanoma, a malignant tumor that originates in melanocytes. It is also associated with a variety of cancers including breast cancer, colorectal cancer and liver cancer. NME1 protects against neurotoxin, alpha-synuclein, and LRRK2-induced neuromutation in a cell model of Parkinson's disease, suggesting that NME1 may play a role in neuroprotection.

Bioapplications of NME1

Because NME1 is associated with tumorigenesis, development, and metastasis, researchers often study its expression patterns and function in different types of cancer. These studies contribute to understanding the molecular mechanisms of cancer and may provide new targets for cancer treatment. A deeper understanding of NME1's function could lead to the development of new drugs, particularly for diseases where NME1 expression or activity is abnormal. For example, the development of small molecule drugs that can regulate the activity of NME1 may be beneficial in the treatment of certain cancers. The detection of NME1 can serve as a cognitive intelligence model segment to help physicians assess disease states, especially in cancer management.

Case Study 1: Imran Khan, 2022

Tumor-derived exosomes have documented roles in accelerating the initiation and outgrowth of metastases, as well as in therapy resistance. Little information supports the converse, that exosomes or similar vesicles can suppress metastasis. The researchers investigated the NME1 (Nm23-H1) metastasis suppressor as a candidate for metastasis suppression by extracellular vesicles. Exosomes derived from two cancer cell lines (MDA-MB-231T and MDA-MB-435), when transfected with the NME1 (Nm23-H1) metastasis suppressor, secreted exosomes with NME1 as the predominant constituent. These exosomes entered recipient tumor cells, altered their endocytic patterns in agreement with NME1 function, and suppressed in vitro tumor cell motility and migration compared to exosomes from control transfectants. Proteomic analysis of exosomes revealed multiple differentially expressed proteins that could exert biological functions. Therefore, they also prepared and investigated liposomes, empty or containing partially purified rNME1. rNME1 containing liposomes recapitulated the effects of exosomes from NME1 transfectants in vitro.

Fig1. Naïve MDA-MB-231T cells were treated with exosomes derived from vector- or NME1 overexpressing MDA-MB-435 or MDA-MB-231T cells and total cellular NME1 expression was assessed by western blots.

Fig2. Control (empty) liposomes and liposomes containing partially purified recombinant rNME1 were assessed for particle size distributions and zeta potential using ZetaView.

Case Study 2: Jin Hyoung Cho, 2021

This study aimed to investigate the effects of the human macrophage (MP) secretome in cellular xenograft rejection. The role of human nucleoside diphosphate kinase A (hNME1), from the secretome of MPs involved in the neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem cells (mp AD-MSCs), was evaluated by proteomic analysis. Herein, this study demonstrates that hNME1 strongly binds to porcine ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (pST8SIA1), which is a ganglioside GD3 synthase. When hNME1 binds with pST8SIA1, it induces degradation of pST8SIA1 in mp AD-MSCs, thereby inhibiting the expression of ganglioside GD3 followed by decreased neuronal differentiation of mp AD-MSCs. Therefore, the researchers produced nanobodies (NBs) named NB-hNME1 that bind to hNME1 specifically, and the inhibitory effect of NB-hNME1 was evaluated for blocking the binding between hNME1 and pST8SIA1. Consequently, NB-hNME1 effectively blocked the binding of hNME1 to pST8SIA1, thereby recovering the expression of ganglioside GD3 and neuronal differentiation of mp AD-MSCs.

Fig3. The schematic structure and production of rhNME1 or His-rhNME1 proteins.

Fig4. Phase-contrast images of cultured mp AD-MSCs and NI-mp AD-MSCs with or without rhNME1 (4 ng/mL).

NME1 has several biochemical functions, for example, ATP binding,GTP binding,deoxyribonuclease activity. Some of the functions are cooperated with other proteins, some of the functions could acted by NME1 itself. We selected most functions NME1 had, and list some proteins which have the same functions with NME1. You can find most of the proteins on our site.

NME1 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with NME1 here. Most of them are supplied by our site. Hope this information will be useful for your research of NME1.

N/A;POLR1C;NME4;NME3