{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FBXO10 is an F‐box protein that functions as the substrate recognition subunit of an SCF (SKP1–Cullin–F‐box) ubiquitin ligase complex, thereby mediating the ubiquitination and subsequent proteasomal degradation of specific target proteins. Several studies have demonstrated that FBXO10 targets the anti‐apoptotic protein BCL2 for degradation, a process that promotes apoptosis in lymphoid cells. Loss or diminished expression of FBXO10 has been observed in certain human B‐cell lymphomas, and this deficiency correlates with aberrantly high levels of BCL2 that favor cell survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In addition, FBXO10 contributes to the regulation of B‐cell receptor signaling; rapid and reversible palmitoylation of the SCF–FBXO10 complex results in its translocation to the cell membrane where it targets the HGAL protein for degradation, thereby dampening BCR‐induced calcium influx and downstream signaling events."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In the nervous system, prokineticin‐2 has been shown to promote FBXO10‐dependent ubiquitination and degradation of ACSL4, which, in turn, limits the accumulation of lipid peroxidation substrates and protects neurons from ferroptotic cell death following traumatic injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, in models of breast cancer susceptibility, differential expression and regulation of FBXO10 in T cells has been implicated in modulating immune‐mediated tumor resistance; here, stress‐induced pathways involving PKC and the AP1 family member c‐Fos have been linked to activation of the FBXO10 promoter."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": " Finally, FBXO10 has been implicated in neuroinflammatory conditions such as depression, where enhanced FBXO10 activity reduces the accumulation of the receptor for advanced glycation end products (RAGE), leading to improvements in behavioral and cognitive outcomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these findings underscore a multifaceted role for FBXO10 as a critical regulator of apoptosis, immune function, and neuronal homeostasis through its ubiquitin ligase activity; dysregulation of FBXO10 may contribute to oncogenesis, altered immune responses, and neurodegenerative processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Michael Chiorazzi, Lixin Rui, Yandan Yang, et al. 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