{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNME2, a multifunctional nucleoside diphosphate kinase, plays a critical role in coordinating several membrane‐associated and cytoplasmic events. For example, it partners with dynamin‐family proteins to load GTP locally and thereby drives endocytic fission and mitochondrial inner‐membrane remodeling, while at the plasma membrane it associates with specific receptors – such as the thromboxane A₂ receptor and estrogen receptor β – and modulates downstream signaling including Rho GTPase activities. In addition, NME2 is found at the cell surface of select leukemia cells and interacts with ion channels (for instance, strengthening TRPV5‐mediated Ca²⁺ reabsorption in kidney epithelia) and transporters such as CFTR, contributing to local energy supply and signal transduction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the nucleus, NME2 functions as a transcriptional regulator with atypical DNA‐binding and enzymatic activities that link its kinase function to genome regulation. It directly binds duplex DNA and even cleaves it via a covalent intermediate, and it occupies key promoter regions such as those of hTERT and c‑Myc by unfolding regulatory G‑quadruplex motifs. Such promoter occupancy recruits repressor complexes (for example, REST–LSD1) or facilitates transcriptional up‐regulation (in conjunction with factors like PIWIL2), while its association with telomeres may serve to inhibit telomerase activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn cancer and other pathological contexts, NME2 has emerged as a double‐edged regulator that can either suppress or promote neoplastic progression depending on cellular context. In neuroblastoma, its expression is up‐regulated downstream of oncogenic N‑myc, while in lung, colorectal, and osteosarcoma models NME2 modulates key determinants of cell proliferation, migration, and chemoresistance – for instance through repression of focal adhesion factors and modulation of MAPK/ERK signaling, through epigenetic alterations, or via interactions with microRNAs that control its tumor‐suppressor functions. Its prognostic relevance is also underscored in hematological malignancies and mesothelioma, and functions affecting angiogenesis (including regulation of Angiopoietin‑2 via FoxO1) further link NME2 to the tumor microenvironment and metastatic potential."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Junko Okabe-Kado, Takashi Kasukabe, Yoshio Honma "}, {"type": "b", "children": [{"type": "t", "text": "Expression of cell surface NM23 proteins of human leukemia cell lines of various cellular lineage and differentiation stages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leuk Res (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0145-2126(01)00171-0"}], "href": "https://doi.org/10.1016/s0145-2126(01"}, {"type": "t", "text": "00171-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12007505"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12007505"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Moulay Driss Rochdi, Geneviève Laroche, Emilie Dupré, et al. 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