{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nZC3HC1 encodes the protein NIPA, which plays a central role in cell cycle regulation. NIPA functions as an F‐box–like subunit of an SCF-type E3 ubiquitin ligase that targets nuclear cyclin B1 for degradation during interphase, thereby preventing premature mitotic entry. In this capacity its activity is precisely controlled by cell‐cycle–dependent phosphorylation. When phosphorylated by kinases such as ERK2, NIPA becomes inactivated during G2/M, allowing cyclin B1 to accumulate and trigger mitosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its fundamental role in cell cycle control, genetic variations in ZC3HC1 have been linked to cardiovascular traits. A common coding polymorphism (rs11556924) results in altered regulatory phosphorylation of NIPA, which in turn modulates nuclear cyclin B1 stability and extends the duration of mitosis. Such changes in cell-cycle dynamics may underlie the observed associations with coronary artery disease, ischemic stroke and hypertension, as evidenced by multiple genetic and epidemiological studies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its enzymatic role in cell cycle progression, ZC3HC1 has been identified as a novel structural component of the nuclear basket. Here, it contributes to the proper recruitment and stable attachment of TPR (a major structural nucleoporin) to the nuclear envelope, suggesting that ZC3HC1 may also influence nuclear architecture and nucleocytoplasmic transport. Furthermore, NIPA has been implicated in antiapoptotic signaling downstream of oncogenic kinases, highlighting its multifunctional nature."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tao Ouyang, Ren-Yuan Bai, Florian Bassermann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of a nuclear interacting partner of anaplastic lymphoma kinase (NIPA)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M300883200"}], "href": "https://doi.org/10.1074/jbc.M300883200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12748172"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12748172"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Florian Bassermann, Christine von Klitzing, Silvia Münch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NIPA defines an SCF-type mammalian E3 ligase that regulates mitotic entry."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2005.04.034"}], "href": "https://doi.org/10.1016/j.cell.2005.04.034"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16009132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16009132"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Christine von Klitzing, Richard Huss, Anna Lena Illert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "APC/C(Cdh1)-mediated degradation of the F-box protein NIPA is regulated by its association with Skp1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0028998"}], "href": "https://doi.org/10.1371/journal.pone.0028998"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22205987"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22205987"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Anna Lena Illert, Michael Zech, Cathrin Moll, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extracellular signal-regulated kinase 2 (ERK2) mediates phosphorylation and inactivation of nuclear interaction partner of anaplastic lymphoma kinase (NIPA) at G2/M."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.373464"}], "href": "https://doi.org/10.1074/jbc.M112.373464"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22955283"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22955283"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Raquel López-Mejías, Fernanda Genre, Mercedes García-Bermúdez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ZC3HC1 rs11556924 polymorphism is associated with increased carotid intima-media thickness in patients with rheumatoid arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arthritis Res Ther (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/ar4335"}], "href": "https://doi.org/10.1186/ar4335"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24286297"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24286297"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Tarja Kunnas, Seppo T Nikkari "}, {"type": "b", "children": [{"type": "t", "text": "Association of Zinc Finger, C3HC-Type Containing 1 (ZC3HC1) rs11556924 Genetic Variant With Hypertension in a Finnish Population, the TAMRISK Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Medicine (Baltimore) (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MD.0000000000001221"}], "href": "https://doi.org/10.1097/MD.0000000000001221"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26266351"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26266351"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Peter D Jones, Michael A Kaiser, Maryam Ghaderi Najafabadi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Coronary Artery Disease-associated Coding Variant in Zinc Finger C3HC-type Containing 1 (ZC3HC1) Affects Cell Cycle Regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.734020"}], "href": "https://doi.org/10.1074/jbc.M116.734020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27226629"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27226629"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Tara Linseman, Sébastien Soubeyrand, Amy Martinuk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional Validation of a Common Nonsynonymous Coding Variant in ZC3HC1 Associated With Protection From Coronary Artery Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circ Cardiovasc Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCGENETICS.116.001498"}], "href": "https://doi.org/10.1161/CIRCGENETICS.116.001498"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28115489"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28115489"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Huijun Ma, Yongjun He, Mei Bai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The genetic polymorphisms of ZC3HC1 and SMARCA4 are associated with hypertension risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Genet Genomic Med (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mgg3.942"}], "href": "https://doi.org/10.1002/mgg3.942"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31507094"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31507094"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Simin Jafaripour, Payam Sasanejad, Malihe Dadgarmoghaddam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ADAMTS7 and ZC3HC1 Share Genetic Predisposition to Coronary Artery Disease and Large Artery Ischemic Stroke."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Crit Rev Eukaryot Gene Expr (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1615/CritRevEukaryotGeneExpr.2019028209"}], "href": "https://doi.org/10.1615/CritRevEukaryotGeneExpr.2019028209"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31679296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31679296"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Philip Gunkel, Haruki Iino, Sandra Krull, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ZC3HC1 Is a Novel Inherent Component of the Nuclear Basket, Resident in a State of Reciprocal Dependence with TPR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells10081937"}], "href": "https://doi.org/10.3390/cells10081937"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34440706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34440706"}]}]}]}