{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Brain expressed X‐linked 3 (BEX3), also known as NGFRAP1, is emerging as a multifunctional modulator in both neural physiology and cancer biology. BEX3 acts as a molecular adaptor that interacts with the p75 neurotrophin receptor to influence nerve growth factor (NGF)–mediated signaling cascades, thereby contributing to the regulation of apoptosis, differentiation, and cell‐cycle events in neural tissues."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, BEX3 has been shown to directly regulate transcription by binding to the promoter region of the TrkA gene; its dimerization and nuclear shuttling enhance both basal and NGF-induced promoter activation, such that downregulation of BEX3 increases neuronal apoptosis and compromises neurite differentiation in cellular models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Beyond its transcriptional role, BEX3 localizes at perinuclear mitochondria during periods of active DNA replication, indicating a contribution to mitochondrial function and growth control, since siRNA-mediated reduction of BEX3 correlates with slowed cellular proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Its expression in mature olfactory receptor neurons further underscores a role in sensory neuron function, as evidenced by its colocalization with olfactory marker protein (OMP)."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, in the context of malignancy, contrasting expression patterns among BEX family members have been observed; while some members such as BEX1 and BEX4 are downregulated in oral squamous cell carcinoma, BEX3 is notably overexpressed in primary tumors, suggesting a distinct, context-dependent contribution to tumor biology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ali Naderi, Andrew E Teschendorff, Juergen Beigel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BEX2 is overexpressed in a subset of primary breast cancers and mediates nerve growth factor/nuclear factor-kappaB inhibition of apoptosis in breast cancer cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-06-4394"}], "href": "https://doi.org/10.1158/0008-5472.CAN-06-4394"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17638883"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17638883"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Laura Calvo, Begoña Anta, Saray López-Benito, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bex3 Dimerization Regulates NGF-Dependent Neuronal Survival and Differentiation by Enhancing trkA Gene Transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4646-14.2015"}], "href": "https://doi.org/10.1523/JNEUROSCI.4646-14.2015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25948268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25948268"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ae-Jung Kim, Cheol-Soon Lee, David Schlessinger "}, {"type": "b", "children": [{"type": "t", "text": "Bex3 associates with replicating mitochondria and is involved in possible growth control of F9 teratocarcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gene (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.gene.2004.08.031"}], "href": "https://doi.org/10.1016/j.gene.2004.08.031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15563833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15563833"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Maik Behrens, Joyce W Margolis, Frank L Margolis "}, {"type": "b", "children": [{"type": "t", "text": "Identification of members of the Bex gene family as olfactory marker protein (OMP) binding partners."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurochem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1471-4159.2003.01940.x"}], "href": "https://doi.org/10.1046/j.1471-4159.2003.01940.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12911636"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12911636"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Wei Gao, John Zeng-Hong Li, Si-Qi Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased brain-expressed X-linked 4 (BEX4) expression promotes growth of oral squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-016-0355-6"}], "href": "https://doi.org/10.1186/s13046-016-0355-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27297407"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27297407"}]}]}]}