{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nInhibitor of growth 4 (ING4) is a chromatin-binding adaptor protein that functions as part of histone acetyltransferase complexes to regulate nucleosomal histone H4 acetylation. This modification underlies its broad influence on cellular processes including DNA repair, cell cycle progression, apoptosis, and tumor suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nING4 also plays a critical role in modulating inflammatory responses. In vivo studies have revealed that deficiency of ING4 leads to exaggerated cytokine production and heightened inflammatory reactions through dysregulation of nuclear factor‑kappa B (NF‑κB) signaling. Notably, ING4 interacts with SIRT1 to restrain NF‑κB activity by limiting both its nuclear translocation and acetylation, thereby mitigating inflammatory injury in sepsis models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, ING4 exerts tumor suppressor effects and helps shape the tumor immune microenvironment. Gene delivery strategies exploiting ING4 have demonstrated promise in glioma therapy by overcoming blood–brain barrier limitations and directly inhibiting tumor growth. Moreover, reduced ING4 levels in head and neck as well as breast cancers correlate with an immune milieu that favors tumor progression and metastasis, highlighting its role in both direct tumor suppression and immune modulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in inflammation and cancer, ING4 is also essential for proper developmental processes. In conjunction with the related protein ING5, ING4 is indispensable for heart development by promoting the formation and function of epicardial and epicardium‐derived cells. Deficiencies in these chromatin-adaptor proteins lead to notable cardiac defects, underscoring their importance in regulating gene expression during embryogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Argyris Tzouvelekis, Vassilis Aidinis, Vagelis Harokopos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Down-regulation of the inhibitor of growth family member 4 (ING4) in different forms of pulmonary fibrosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Respir Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1465-9921-10-14"}], "href": "https://doi.org/10.1186/1465-9921-10-14"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19250543"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19250543"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Andrew H Coles, Hugh Gannon, Anna Cerny, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibitor of growth-4 promotes IkappaB promoter activation to suppress NF-kappaB signaling and innate immunity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0912116107"}], "href": "https://doi.org/10.1073/pnas.0912116107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20534538"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20534538"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yunshu Yang, Yang Liu, Xiang He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ING4 alleviated lipopolysaccharide-induced inflammation by regulating the NF-κB pathway via a direct interaction with SIRT1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunol Cell Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/imcb.12308"}], "href": "https://doi.org/10.1111/imcb.12308"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31811786"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31811786"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Shanshan Wang, Sören Reinhard, Chengyi Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Antitumoral Cascade-Targeting Ligand for IL-6 Receptor-Mediated Gene Delivery to Glioma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Ther (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ymthe.2017.04.023"}], "href": "https://doi.org/10.1016/j.ymthe.2017.04.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28502470"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28502470"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhi Cui, Shiqun Sun, Jia Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibitor of Growth 4 (ING4) Plays a Tumor-repressing Role in Oral Squamous Cell Carcinoma via Nuclear Factor Kappa-B (NF-kB)/DNA Methyltransferase 1 (DNMT1) Axis-mediated Regulation of Aldehyde Dehydrogenase 1A2 (ALDH1A2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Cancer Drug Targets (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2174/1568009622666220406104732"}], "href": "https://doi.org/10.2174/1568009622666220406104732"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35388759"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35388759"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Emily Tsutsumi, Anne M Macy, Janine LoBello, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor immune microenvironment permissive to metastatic progression of ING4-deficient breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0304194"}], "href": "https://doi.org/10.1371/journal.pone.0304194"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38968186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38968186"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Sophia Y Y Mah, Hannah K Vanyai, Connie S N Li-Wai-Suen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ING4 and ING5 are essential for histone H3 lysine 14 acetylation and epicardial cell lineage development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Development (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/dev.202617"}], "href": "https://doi.org/10.1242/dev.202617"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38446206"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38446206"}]}]}]}