{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DCAF13 functions as a multifaceted regulator by serving as a substrate receptor for CRL4 ubiquitin ligase complexes in diverse biological contexts. In oocytes, DCAF13 is a critical nucleolar component that participates in the processing of ribosomal RNA—particularly the maturation of 18S rRNA—and is essential for the chromatin configuration transition (NSN‐to‐SN) that permits proper oocyte development and protein synthesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In early embryos, DCAF13 acts as a novel CRL4 adaptor that mediates the polyubiquitination and proteasomal degradation of key epigenetic regulators such as SUV39H1, thereby enabling the removal of repressive H3K9 trimethylation marks to ensure appropriate zygotic gene activation and overall embryonic progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In maturing oocytes, DCAF13 further promotes meiotic resumption by facilitating the degradation of PTEN, which in turn sustains PI3K pathway activity and proper cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n DCAF13 also plays a prominent role in oncogenesis. Its overexpression is frequently observed in hepatocellular carcinoma, where it correlates with poor tumor grade, deregulation of cell cycle progression, and adverse patient survival outcomes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In breast cancer, particularly within triple‐negative subtypes, DCAF13 exerts additional oncogenic effects by acting as an RNA binding protein: it binds to AU‐rich elements in target mRNAs (for example, DTX3) to facilitate their degradation, which in turn results in the activation of NOTCH4 signaling and promotes epithelial–mesenchymal transition, cell migration, and invasion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "and."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, DCAF13 influences cancer cell proliferation and survival by modulating the stability of key apoptotic effectors, such as PERP, thereby linking its regulatory function to cell cycle arrest and senescence in breast cancer models."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n A genetic variant in DCAF13 has also been identified in familial cortical myoclonic tremor with epilepsy, suggesting that alterations in this gene may contribute to neurological disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In colorectal cancer treated with immunotherapy, upregulation of DCAF13 has been associated with activation of tumor survival pathways and chemoresistance, emphasizing its emerging role as a potential diagnostic marker and therapeutic target in multiple cancer types."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Additionally, in osteosarcoma, DCAF13 has been found as a component of a complex with CUL4B and DDB1, further underscoring its involvement in cell cycle regulation and tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jue Zhang, Yin-Li Zhang, Long-Wen Zhao, et al. 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