{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMenin, the protein product of the MEN1 gene, is a critical tumor suppressor that orchestrates gene transcription through epigenetic regulation in endocrine tissues. By serving as a scaffold for multiprotein complexes—most notably those containing mixed‐lineage leukemia (MLL) histone methyltransferases—menin promotes histone H3 lysine 4 methylation, thereby activating homeobox genes and cyclin-dependent kinase inhibitors essential for controlled cell proliferation and differentiation. Germline and somatic MEN1 mutations disrupt these interactions and downstream transcriptional programs, contributing to neoplasia in the parathyroids, pancreatic islets, and anterior pituitary, among other endocrine organs."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMenin’s functions extend beyond tumor suppression in endocrine tissues; it also acts as an essential cofactor in several oncogenic contexts. Notably, in MLL‐fusion driven leukemias and androgen receptor–mediated prostate cancer, menin interacts directly with transcription factors such as JunD, LEDGF, and c‐Myc to modulate gene expression. This dual nature—functioning as a transcriptional activator or repressor depending on its binding partners—accounts for its paradoxical role in promoting leukemogenesis in some settings while suppressing tumorigenesis in others. Moreover, altered menin function has been implicated in the development of resistance to targeted menin–MLL inhibitors, underscoring its centrality in diverse cellular pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "28"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther broadening its biological reach, menin contributes to cellular differentiation and the maintenance of genomic stability. In pancreatic neuroendocrine tumors, menin loss is associated with deregulated β‐catenin signaling and aberrant epigenetic states, while its direct binding to double‐stranded DNA and interaction with replication protein complexes emphasize a role in DNA repair and replication. In addition, menin modulates differentiation programs—as seen in osteoblast commitment—and controls the expression of genes fundamental to lineage specification, thereby dictating tissue-specific tumor phenotypes. These functions are critically disrupted by MEN1 mutations that impair menin’s stability, protein–protein interactions, or DNA association."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "29", "end_ref": "38"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent advances have further refined our understanding of menin’s clinical and therapeutic implications. Enhanced genetic screening has improved the identification of MEN1 mutations in diverse patient populations, while innovative small‐molecule inhibitors that disrupt the menin–MLL interaction show potent antitumor activity in preclinical models. Nonetheless, resistance mutations at the inhibitor–menin interface and the complex interplay of menin with various signaling cascades continue to pose challenges for clinical translation. These insights underscore the importance of continued research into menin’s DNA binding properties and its multifaceted role in cellular homeostasis for developing tailored therapeutic strategies in MEN1‐associated disorders."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "39", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bruno Vergès, Françoise Boureille, Pierre Goudet, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The 32-kilodalton subunit of replication protein A interacts with menin, the product of the MEN1 tumor suppressor gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.23.2.493-509.2003"}], "href": "https://doi.org/10.1128/MCB.23.2.493-509.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12509449"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12509449"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hyungsoo Kim, Ji-Eun Lee, Eun-Jung Cho, et al. 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