{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ANAPC2 encodes a core subunit of the anaphase‐promoting complex/cyclosome (APC/C), an essential E3 ubiquitin ligase that orchestrates the timely degradation of key cell cycle regulators. Several studies have highlighted its multifaceted roles in cell cycle control and tumor biology. For instance, in renal cell carcinoma models, downregulation of G1 phase–related genes—including ANAPC2—upon STAT1 knockdown was associated with altered cell cycle dynamics and increased sensitivity to chemoradiotherapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Similarly, experiments in vascular smooth muscle cells showed that reduction of adhesion protein Talin‐1 led to an upregulation of ANAPC2, suggesting that extracellular matrix signals can indirectly modulate APC/C activity and cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of reproductive biology, loss‐of‐function studies in human spermatogenesis identified ANAPC2 as one of the APC/C subunits that interacts with FBXO43, with its proper function being essential for progression through meiosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, epigenetic analyses in first‐trimester placentae demonstrated differential methylation at the ANAPC2 locus between in vitro fertilization and non‐IVF conceptions, hinting at a possible role in placental development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Broader investigations into ubiquitin‐mediated protein degradation in diverse species have grouped ANAPC2 with other genes involved in maintaining proteostasis under stress conditions, such as during heat adaptation in aquatic species."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " In colorectal cancer, combination therapies that simultaneously target Wnt signaling and utilize small molecules have been shown to elevate ANAPC2 expression, promoting the ubiquitination and subsequent degradation of oncogenic KRAS; this observation underscores the potential of manipulating ANAPC2 activity to reduce oncogenic signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, comprehensive reviews of the APC/C complex emphasize that subunits such as ANAPC2 are indispensable for maintaining genomic integrity, regulating cell cycle progression, and suppressing tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Collectively, these findings illustrate that ANAPC2’s function is tightly interwoven with ubiquitin‐dependent proteolysis, serving as a critical nexus in cell cycle regulation, developmental processes, and the response to therapeutic interventions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hongxia Zhu, Zaozao Wang, Qing Xu, et al. 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