{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HDGFL3, also known as hepatoma‐derived growth factor‐related protein 3 (HRP3), has emerged as a multifunctional factor that integrates chromatin binding with diverse signaling roles across several biological systems. Structural and biochemical studies have shown that its N‐terminal PWWP domain simultaneously engages both double‐stranded DNA (with a preference for a narrow minor groove) and methylated histone marks (notably H3K36me2/3), thereby mediating high‐affinity chromatin recruitment and influencing transcriptional programs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In cancer settings, particularly hepatocellular carcinoma and certain lymphomas, HDGFL3 contributes to tumorigenesis by promoting cell proliferation, survival, and resistance to apoptotic stimuli; in lung cancer models, knockdown experiments have implicated HDGFL3 in modulating radio‐ and chemoresistance via regulation of reactive oxygen species and antioxidant pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the nervous system, HDGFL3 assumes distinct neurotrophic roles by supporting neuronal survival and neurite outgrowth, with studies in primary cortical neurons and developmental models underscoring its importance for proper neuronal differentiation and myelination during development and repair."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Additionally, its identification as an endothelial ligand with potent pro-angiogenic activity—capable of stimulating endothelial cell migration, tube formation, and sprouting—further highlights HDGFL3’s versatility in modulating both intrinsic gene expression and extrinsic signaling cascades that govern tissue vascularization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these findings position HDGFL3 as a key mediator at the crossroads of epigenetic regulation, cellular proliferation, stress response, and tissue remodeling. This integrated function not only illuminates its contributions to developmental and repair processes but also underscores its potential as a therapeutic target in cancer, neurodegeneration, and angiogenesis‐related pathologies.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wei Tian, Peiqiang Yan, Ning Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The HRP3 PWWP domain recognizes the minor groove of double-stranded DNA and recruits HRP3 to chromatin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkz294"}], "href": "https://doi.org/10.1093/nar/gkz294"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31162607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31162607"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Heba M Eltahir "}, {"type": "b", "children": [{"type": "t", "text": "Insight into the roles of hepatoma derived growth factor related protein-3 under physiological and pathological conditions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Cell Biol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1139/bcb-2018-0098"}], "href": "https://doi.org/10.1139/bcb-2018-0098"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30074399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30074399"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hong Shik Yun, Eun-Hee Hong, Su-Jae Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Depletion of hepatoma-derived growth factor-related protein-3 induces apoptotic sensitization of radioresistant A549 cells via reactive oxygen species-dependent p53 activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2013.08.086"}], "href": "https://doi.org/10.1016/j.bbrc.2013.08.086"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24012673"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24012673"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Hong Shik Yun, Jeong-Hwa Baek, Ji-Hye Yim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of hepatoma-derived growth factor-related protein-3 induces apoptosis of H1299 cells via ROS-dependent and p53-independent NF-κB activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2014.05.039"}], "href": "https://doi.org/10.1016/j.bbrc.2014.05.039"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24857986"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24857986"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Mekky M Abouzied, Heba M El-Tahir, Volkmar Gieselmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatoma-derived growth factor-related protein-3: a new neurotrophic and neurite outgrowth-promoting factor for cortical neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jnr.22507"}], "href": "https://doi.org/10.1002/jnr.22507"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20890995"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20890995"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Bilal Ersen Kerman, Stéphane Genoud, Burcu Kurt Vatandaslar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Motoneuron expression profiling identifies an association between an axonal splice variant of HDGF-related protein 3 and peripheral myelination."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA120.014329"}], "href": "https://doi.org/10.1074/jbc.RA120.014329"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32647008"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32647008"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Michelle E LeBlanc, Weiwen Wang, Nora B Caberoy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatoma-derived growth factor-related protein-3 is a novel angiogenic factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0127904"}], "href": "https://doi.org/10.1371/journal.pone.0127904"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25996149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25996149"}]}]}]}