{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Anaphase‐promoting complex subunit 7 (APC7) is a conserved, tetratricopeptide repeat–containing component of the anaphase‐promoting complex/cyclosome (APC/C), an E3 ubiquitin ligase that governs key cell cycle transitions by targeting proteins such as securin and cyclin‐B for ubiquitination and degradation (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Alterations in APC7 expression have been linked to tumor biology. For example, microarray analyses in cisplatin‐resistant bladder cancer identified several cell cycle–associated genes, including APC7, as being significantly upregulated"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", whereas immunohistochemical studies in breast cancer revealed that loss of APC7 expression is more frequent in carcinomas with high histologic and nuclear grades and in tumors with high proliferative indices."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Structural studies have further detailed that APC7, although lacking the canonical TPR consensus sequences, adopts a TPR-like fold and forms a unique homodimer interface that may be critical for binding adaptor proteins and substrates within the APC/C complex."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its canonical role in the regulation of mitosis, APC7 has been implicated in non–cell cycle functions. In a yeast two-hybrid screen investigating IL-17 receptor signaling, APC7 (also referred to as AnapC7) was identified as an interaction partner of both IL-17RA and IL-17RC; however, its knockdown did not markedly impact IL-17–mediated gene expression, suggesting that its mere binding does not equate to functional indispensability in that pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its protein-coding role, transcripts derived from the APC7 gene have gained attention in the form of circular RNAs. In pancreatic cancer, circANAPC7 was shown to function as a microRNA sponge for miR-373, leading to enhanced PHLPP2-mediated dephosphorylation of AKT and subsequent down-regulation of cyclin D1 and transforming growth factor–β, thereby suppressing tumor growth and muscle wasting."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Similarly, in acute myeloid leukemia (AML), circ-ANAPC7 is upregulated and correlates with higher peripheral white blood cell counts and bone marrow blast percentages, indicating its potential as a biomarker for disease diagnosis and monitoring."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, APC7 has emerged in other biological and pathological contexts. It appears as a hub gene in protein-protein interaction analyses of exosomal circular RNA networks in ischemic stroke"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "and as a candidate immune-related gene in genetic studies on susceptibility to respiratory pathogens in sheep."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Proteomic analyses in porcine intestinal epithelial cells infected with PDCoV verified the downregulation of APC7 during infection"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and separate gene expression studies in mouse models of depression noted a downregulation of Anapc7 associated with altered cell proliferation and cell survival pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, APC7 has also been targeted experimentally; for instance, an AID-nanobody approach was successfully employed to conditionally and reversibly inactivate the entire APC/C complex—including APC7—in human cells and zebrafish, thereby underscoring its utility in functional dissection of this essential ubiquitin ligase."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight the multifaceted roles of APC7 both as an integral component of the APC/C complex regulating cell cycle progression and as a source of regulatory circular RNAs with tumor suppressor functions. Its dysregulation is implicated in various diseases, including cancer, viral pathogenesis, and neurological disorders, thereby establishing APC7 as a significant molecule in both fundamental cell biology and translational research."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "5", "end_ref": "7"}, {"type": "fg_fs", "start_ref": "9", "end_ref": "11"}, {"type": "fg_f", "ref": "8"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dohyun Han, Kyunggon Kim, Yeonjung Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of the N-terminal domain of anaphase-promoting complex subunit 7."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M804887200"}], "href": "https://doi.org/10.1074/jbc.M804887200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19091741"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19091741"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhuan Zhou, Mingjing He, Anil A Shah, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Insights into APC/C: from cellular function to diseases and therapeutics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Div (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13008-016-0021-6"}], "href": "https://doi.org/10.1186/s13008-016-0021-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27418942"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27418942"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Sung Han Kim, Jin-Nyoung Ho, Hyunjin Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Upregulated expression of BCL2, MCM7, and CCNE1 indicate cisplatin-resistance in the set of two human bladder cancer cell lines: T24 cisplatin sensitive and T24R2 cisplatin resistant bladder cancer cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Investig Clin Urol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4111/icu.2016.57.1.63"}], "href": "https://doi.org/10.4111/icu.2016.57.1.63"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26966728"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26966728"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kwang-Hwa Park, Sung-E Choi, Minseob Eom, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of the anaphase-promoting complex (APC)7 in invasive ductal carcinomas of the breast and its clinicopathologic relationships."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Breast Cancer Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/bcr978"}], "href": "https://doi.org/10.1186/bcr978"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15743504"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15743504"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Allen W Ho, Abhishek V Garg, Leticia Monin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The anaphase-promoting complex protein 5 (AnapC5) associates with A20 and inhibits IL-17-mediated signal transduction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0070168"}], "href": "https://doi.org/10.1371/journal.pone.0070168"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23922952"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23922952"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xiuhui Shi, Jingxuan Yang, Mingyang Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circular RNA ANAPC7 Inhibits Tumor Growth and Muscle Wasting via PHLPP2-AKT-TGF-β Signaling Axis in Pancreatic Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2022.02.017"}], "href": "https://doi.org/10.1053/j.gastro.2022.02.017"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35176309"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35176309"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ying Shen, Yachun Jia, Ru Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Using Circ-ANAPC7 as a Novel Type of Biomarker in the Monitoring of Acute Myeloid Leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Haematol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000520446"}], "href": "https://doi.org/10.1159/000520446"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34879367"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34879367"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hongli Chen, Tian Liu, Jing Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circ-ANAPC7 is Upregulated in Acute Myeloid Leukemia and Appears to Target the MiR-181 Family."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Physiol Biochem (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000491468"}], "href": "https://doi.org/10.1159/000491468"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29969755"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29969755"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Bingyi Xu, Xianli Huang, Yan Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of expression profiles and bioinformatics suggests that plasma exosomal circular RNAs may be involved in ischemic stroke in the Chinese Han population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Metab Brain Dis (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11011-021-00894-2"}], "href": "https://doi.org/10.1007/s11011-021-00894-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35067794"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35067794"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Michelle R Mousel, Stephen N White, Maria K Herndon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genes involved in immune, gene translation and chromatin organization pathways associated with Mycoplasma ovipneumoniae presence in nasal secretions of domestic sheep."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0247209"}], "href": "https://doi.org/10.1371/journal.pone.0247209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34252097"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34252097"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xinrong Zhou, Lei Zhou, Xinna Ge, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Quantitative Proteomic Analysis of Porcine Intestinal Epithelial Cells Infected with Porcine Deltacoronavirus Using iTRAQ-Coupled LC-MS/MS."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Proteome Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/acs.jproteome.0c00592"}], "href": "https://doi.org/10.1021/acs.jproteome.0c00592"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33045833"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33045833"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "R M Tordera, A L Garcia-García, N Elizalde, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Chronic stress and impaired glutamate function elicit a depressive-like phenotype and common changes in gene expression in the mouse frontal cortex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur Neuropsychopharmacol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.euroneuro.2010.06.016"}], "href": "https://doi.org/10.1016/j.euroneuro.2010.06.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20937555"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20937555"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Katrin Daniel, Jaroslav Icha, Cindy Horenburg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Conditional control of fluorescent protein degradation by an auxin-dependent nanobody."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-05855-5"}], "href": "https://doi.org/10.1038/s41467-018-05855-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30120238"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30120238"}]}]}]}