{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNDN is a paternally expressed, maternally imprinted gene whose product, necdin, plays critical roles during neurodevelopment. Early studies localized NDN to the Prader–Willi syndrome (PWS) critical region and showed that necdin is predominantly expressed in differentiated neurons, where it appears to promote cell cycle arrest and support proper neuronal differentiation and survival. In addition, loss of NDN expression is implicated in several PWS phenotypes—including aberrant brain development, impaired migration of gonadotropin‐releasing hormone neurons, and features of sensory–motor deficits—while genetic variants in NDN have been associated with neurodevelopmental and psychiatric features such as SMS‐like symptoms and paranoid thinking."}, {"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": "\nBeyond its developmental role, necdin functions as a potent regulator of cellular growth, survival, and tumor suppression. It has been shown to bind intracellular mediators—including the IL-1α precursor, p53, and transcription factors like E2F-1—and negatively regulate pro-growth signals. Moreover, necdin interacts with HIF-1α to modulate its stability and exerts STAT3-dependent transcriptional repression. In several cancer types ranging from colorectal and ovarian carcinoma to breast and head and neck cancers, downregulation of NDN via genetic loss or promoter hypermethylation correlates with increased proliferation, invasion, and metastasis, supporting its role as a tumor suppressor. Comprehensive interactome analyses further reveal that necdin engages with ubiquitin regulatory proteins and chromatin modifiers, underscoring its involvement in diverse epigenetic and signaling pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in transcriptional regulation and growth control, necdin modulates cytoskeletal dynamics, cell polarity, and differentiation in diverse cell types. It can influence neurite outgrowth by binding proteins such as Nogo-A and is involved in maintaining proper adhesion and migration in neuronal and non-neuronal cells. Moreover, necdin inhibits adipogenic differentiation in pre-adipocytes and promotes the survival of myogenic precursors by targeting pro-apoptotic factors. Although the precise mechanisms controlling its nuclear–cytoplasmic shuttling remain to be fully elucidated, these studies underscore a broad contribution of NDN to the regulation of cellular architecture and motility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "23", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "H R MacDonald, R Wevrick "}, {"type": "b", "children": [{"type": "t", "text": "The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (1997)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/6.11.1873"}], "href": "https://doi.org/10.1093/hmg/6.11.1873"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9302265"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9302265"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "F Oeffner, T Korn, H Roth, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Systematic screening for mutations in the human necdin gene (NDN): identification of two naturally occurring polymorphisms and association analysis in body weight regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Obes Relat Metab Disord (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.ijo.0801626"}], "href": "https://doi.org/10.1038/sj.ijo.0801626"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11439287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11439287"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jason C Y Lau, Meredith L Hanel, Rachel Wevrick "}, {"type": "b", "children": [{"type": "t", "text": "Tissue-specific and imprinted epigenetic modifications of the human NDN gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkh671"}], "href": "https://doi.org/10.1093/nar/gkh671"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15247330"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15247330"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sébastien Zanella, Françoise Watrin, Saïda Mebarek, et al. 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