{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FBXW10 is an F‐box protein that functions as a substrate recognition subunit within SCF‐type E3 ubiquitin ligase complexes, thereby mediating the proteasomal degradation of specific regulatory proteins in a variety of cellular contexts. In cells expressing lamin A mutants, FBXW10 is transcriptionally induced and its ectopic expression leads to the selective degradation of heterochromatin proteins HP1α and HP1β, as well as of the key DNA damage sensor ATR kinase, implicating FBXW10 in aberrant chromatin organization and compromised DNA repair when nuclear lamina integrity is disrupted."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n In hepatocellular carcinoma, high FBXW10 expression is associated with poor prognosis—especially in male patients—where it promotes tumorigenesis by enhancing cell proliferation and migration."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In parallel, studies of ccRCC have demonstrated that FBXW10 is epigenetically regulated via hypermethylation of its differentially methylated region, a modification that is reversible upon treatment with a demethylating agent, pointing to a role in cancer progression through epigenetic mechanisms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, FBXW10 expression is subject to post‐translational regulation: increased global O‑GlcNAcylation results in marked downregulation of FBXW10 at both the mRNA and protein levels, suggesting that O‑GlcNAc modification modulates the ubiquitination machinery by controlling FBXW10 abundance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In T‑prolymphocytic leukemia, recurrent mutations in FBXW10 have been identified, indicating that alterations in its function could contribute to leukemogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In lung squamous cell carcinoma, treatment with the HDAC inhibitor belinostat results in the upregulation of FBXW10 (along with FBXO3), which then targets the son of sevenless (SOS) protein for proteasomal degradation, leading to suppression of the MAPK pathway and enhanced cytotoxicity in combination with cisplatin."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, differential expression of FBXW10 has also been observed in skeletal muscle gene expression profiles following bariatric surgery, suggesting that FBXW10 may contribute to the regulation of protein turnover in metabolic contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Pankaj Chaturvedi, Veena K Parnaik "}, {"type": "b", "children": [{"type": "t", "text": "Lamin A rod domain mutants target heterochromatin protein 1alpha and beta for proteasomal degradation by activation of F-box protein, FBXW10."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0010620"}], "href": "https://doi.org/10.1371/journal.pone.0010620"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20498703"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20498703"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bhattiprolu Muralikrishna, Pankaj Chaturvedi, Kirti Sinha, et al. 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