{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FBXL20 is an F‐box protein that functions as a substrate recognition component of the SCF (Skp1–Cullin1–F‐box) E3 ubiquitin ligase complex and has emerged as a versatile regulator of protein turnover in multiple biological contexts. In response to DNA damage, FBXL20—whose expression is induced in a p53‐dependent manner—targets the lipid kinase Vps34 for polyubiquitination and proteasomal degradation, leading to inhibition of autophagy and receptor endocytosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In hematologic malignancies such as cytogenetically normal acute myeloid leukemia, FBXL20 is directly regulated by miR‐3151, suggesting that its expression is integrated within microRNA‐mediated oncogenic networks."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In solid tumors, FBXL20 appears to play a multifaceted role. Its upregulation in colorectal adenocarcinoma is associated with deregulation of the Wnt/β‐catenin signaling pathway and altered caspase activation, which together contribute to carcinogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, FBXL20 promotes cancer cell survival by directing the proteasomal degradation of key proapoptotic regulators such as PUMA and BAX in an AKT1‐dependent manner, thereby facilitating tumor growth and chemoresistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In ovarian cancer, its expression is negatively regulated by miR‐195–5p; elevated levels of FBXL20 are correlated with enhanced proliferation, accelerated cell cycle progression, and reduced apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In pancreatic cancer, FBXL20 mediates the degradation of oncogenic substrates such as PR55α in a p53‐dependent process, linking tumor suppressor pathways to the control of protein stability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the nervous system, FBXL20 has also been implicated in regulating neuronal excitability. Studies indicate that reduced FBXL20 levels are accompanied by increased expression of the synaptic regulatory protein RIM1, with potential consequences for seizure threshold modulation in epilepsy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Additionally, FBXL20 has been shown to mediate the polyubiquitination of the T cell co-stimulatory receptor 4–1BB, thereby controlling its protein abundance and influencing immune activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies illustrate that FBXL20 acts as a context-dependent regulator of substrate stability, impacting processes such as autophagy, apoptosis, cell cycle progression, and immune as well as synaptic functions. Its diverse roles in modulating key signaling pathways in cancer, neurodegeneration, and immunity highlight FBXL20 as a promising therapeutic target in a variety of human disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Juan Xiao, Tao Zhang, Daichao Xu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "miR-3151 interplays with its host gene BAALC and independently affects outcome of patients with cytogenetically normal acute myeloid leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-02-408492"}], "href": "https://doi.org/10.1182/blood-2012-02-408492"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22529287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22529287"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jianjun Zhu, Kai Li, Lei Dong, et al. 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