{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPRUNE1, whose protein product (h‐prune) plays a pivotal role in oncogenesis, has been shown to promote cell migration, invasion, and metastasis across several tumor types. In multiple studies, h‐prune was found to interact with key signaling proteins such as glycogen synthase kinase‐3 (GSK‐3), focal adhesion kinase (FAK), Rac, and the metastasis suppressor Nm23‐H1, thereby regulating focal adhesion disassembly and epithelial–mesenchymal transition. These interactions underlie its ability to enhance tumor aggressiveness in cancers including breast (15671547), colorectal liver metastasis (16428445, 25026278, 27037526), anaplastic thyroid carcinoma (27109060), medulloblastoma (29490009) and even multiple myeloma (37666675)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOn a mechanistic level, PRUNE1 belongs to the DHH phosphoesterase superfamily and harbors enzymatic domains that confer both exopolyphosphatase and cyclic AMP‐phosphodiesterase activities. Detailed structural and biochemical analyses have mapped its catalytic activity to the N‐terminal region, while independent domains mediate homodimerization and interactions with proteins such as Nm23‐H1. This multifaceted enzymatic function not only influences purine metabolism and WNT/β‐catenin signaling but also modulates cytoskeletal dynamics through effects on microtubule polymerization—a process critical for cell division, migration, and the maintenance of cellular architecture."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel to its oncogenic role, mutations in PRUNE1 have been identified as the genetic basis of a severe autosomal recessive neurodevelopmental and neurodegenerative syndrome. Patients harboring bi‐allelic mutations exhibit a spectrum of neurological deficits including primary microcephaly, global developmental delay, and, in some cases, features of motor neuron involvement and dystonia. Functional assays of disease‐associated variants indicate that these mutations disrupt normal exopolyphosphatase activity and destabilize PRUNE1’s structure, thereby impairing microtubule dynamics essential for proper neuronal differentiation and cortical development. These findings have been consistently reported across several cohorts and studies, expanding the clinical spectrum of PRUNE1‐related disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_fs", "start_ref": "12", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Massimo Zollo, Alessandra Andrè, Antonio Cossu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.26.3.898-911.2006"}], "href": "https://doi.org/10.1128/MCB.26.3.898-911.2006"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16428445"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16428445"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Marianeve Carotenuto, Emilia Pedone, Donatella Diana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuroblastoma tumorigenesis is regulated through the Nm23-H1/h-Prune C-terminal interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep01351"}], "href": "https://doi.org/10.1038/srep01351"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23448979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23448979"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Marianeve Carotenuto, Pasqualino De Antonellis, Lucia Liguori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "H-Prune through GSK-3β interaction sustains canonical WNT/β-catenin signaling enhancing cancer progression in NSCLC."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.2169"}], "href": "https://doi.org/10.18632/oncotarget.2169"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25026278"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25026278"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Masakazu Hashimoto, Tsuyoshi Kobayashi, Hirotaka Tashiro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "h-Prune is associated with poor prognosis and epithelial-mesenchymal transition in patients with colorectal liver metastases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.30118"}], "href": "https://doi.org/10.1002/ijc.30118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27037526"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27037526"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Junko Nambu, Tsuyoshi Kobayashi, Masakazu Hashimoto, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "PRUNE1 (located on chromosome 1q21.3) promotes multiple myeloma with 1q21 Gain by enhancing the links between purine and mitochondrion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Haematol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/bjh.19088"}], "href": "https://doi.org/10.1111/bjh.19088"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37666675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37666675"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Sabine Middelhaufe, Livia Garzia, Uta-Maria Ohndorf, et al. 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