{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BAG4, also known as the silencer of death domains (SODD), has emerged as an important multifunctional protein with diverse roles in regulating apoptosis, RNA processing, and oncogenic transformation. In several studies, BAG4 has been identified as a negative regulator of death receptor signaling. Overexpression of BAG4/SODD can inhibit the spontaneous activation of tumor necrosis factor receptor 1 (TNFR1) and modulate the activity of other death receptors such as CD95, thereby reducing cell sensitivity to apoptosis‐inducing stimuli (see"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In addition, BAG4 has been characterized as a binding partner of apobec-1, where it negatively regulates apoB mRNA editing by altering the chaperone-dependent intranuclear assembly of the editosome, thus highlighting a role in RNA processing."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in regulating apoptotic signaling and RNA editing, BAG4 has also been implicated as an oncogene in various cancer types. In breast and gastric cancers, genomic amplification involving the 8p11-p12 region has led to the overexpression of BAG4, where it contributes to cell transformation, proliferation, and invasion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In colorectal cancer, BAG4 is among the key targets up-regulated through a microRNA-mediated regulatory network, suggesting that loss of microRNA repression may further contribute to its oncogenic function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Moreover, modulation of BAG4 levels by microRNAs, such as miR-194-5p, further supports its role in maintaining an anti-apoptotic state in cancer cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings indicate that BAG4 functions as a safeguard against premature cell death by interfering with death receptor signaling and by regulating the intracellular localization of key RNA editing enzymes, while its deregulation in cancer supports enhanced cell survival and aggressive tumor phenotypes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hedda Eichholtz-Wirth, Eberhard Fritz, Lucie Wolz "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of the 'silencer of death domain', SODD/BAG-4, modulates both TNFR1- and CD95-dependent cell death pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0304-3835(03)00009-0"}], "href": "https://doi.org/10.1016/s0304-3835(03"}, {"type": "t", "text": "00009-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12706861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12706861"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Robert Endres, Georg Häcker, Inge Brosch, et al. 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