{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Inhibitor of growth 2 (ING2) is a multifunctional tumor suppressor that integrates chromatin‐based signaling with p53‐dependent transcriptional control, DNA repair, senescence, and apoptosis. Its plant homeodomain (PHD) finger specifically binds the histone H3 tail when trimethylated at lysine 4 (H3K4me3), thereby targeting ING2 to active chromatin regions and facilitating the recruitment of chromatin‐modifying complexes that are essential for proper gene regulation and apoptotic induction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " ING2 also functions as a cofactor for p53: by enhancing p53 acetylation and transcriptional activity, it contributes to cell cycle arrest and promotes apoptosis in response to DNA damage and cellular stress"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, structural determinants such as a leucine zipper–like motif enable ING2 to act as a scaffold that bridges the interaction between p53 and p300, thereby modulating chromatin remodeling and facilitating efficient nucleotide excision repair, especially following UV irradiation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Altered expression of ING2 has been implicated in tumorigenesis; for instance, reduced nuclear ING2 expression is observed in lung cancer and melanoma, correlating with loss of its tumor suppressive activity, while in colorectal cancer, aberrant upregulation of ING2 has been linked to enhanced expression of matrix metalloproteinases and increased cellular invasiveness"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In mouse models, deficiency of Ing2 leads to defective spermatogenesis and an increased incidence in soft-tissue sarcomas, underscoring its physiological importance in both reproductive biology and tumor suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, ING2’s binding to the nuclear phosphoinositide PtdIns(5)P is critical for its localization and stable association with target gene promoters in response to DNA damage, highlighting a lipid-mediated mechanism that modulates its gene repressive functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pedro V Peña, Foteini Davrazou, Xiaobing Shi, et al. 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