{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FBXO9, an F‐box only protein that serves as the substrate recognition subunit of an SCF (Skp1–Cullin–F‐box) E3 ubiquitin ligase complex, plays multifaceted roles in regulating protein stability in distinct biological contexts. In the adipogenic setting, FBXO9 directly interacts with and ubiquitinates peroxisome proliferator‐activated receptor γ (PPARγ), thereby reducing its protein stability and suppressing adipocyte differentiation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In a parallel study, FBXO9 expression was found to be elevated in obese mice and during the early stages of 3T3‐L1 adipocyte differentiation; moreover, siRNA‐mediated FBXO9 knockdown drastically inhibited adipogenesis through a concomitant decrease in C/EBPβ levels, an effect that could be rescued by forced C/EBPβ expression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Beyond metabolism, FBXO9 has been implicated in modulating components of the innate immune response; loss‐of‐function screening in macrophages identified FBXO9 as one of several genes whose inhibition blocked interleukin‐6 production, suggesting a contributory role in pro‐inflammatory signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the context of human disease, FBXO9 has also emerged as a potential biomarker in viral pathology; transcriptomic analyses in HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP) identified FBXO9 among a set of candidate genes involved in disease progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Moreover, reviews summarizing F‐box protein functions in cancer have noted that FBXO9 may exhibit oncogenic behavior in certain tumors through its regulation of substrates critical for cell proliferation and survival, thereby presenting a potential target for anticancer therapies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the importance of FBXO9 as a regulator of key signaling proteins through ubiquitination, influencing processes such as adipocyte differentiation, immune response modulation, and tumor progression. Its context-dependent roles make FBXO9 a promising candidate for targeted interventions in metabolic disorders, inflammatory conditions, and cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kyeong Won Lee, Soo Heon Kwak, Young Do Koo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "F-box only protein 9 is an E3 ubiquitin ligase of PPARγ."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Mol Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emm.2016.31"}], "href": "https://doi.org/10.1038/emm.2016.31"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27197753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27197753"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Kyeong Won Lee, Soo Heon Kwak, Byung Yong Ahn, et al. 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