{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cytidine monophosphate kinase‐1 (CMPK1) is a multifunctional enzyme that plays key roles in cellular nucleotide metabolism, cancer cell bioenergetics, drug activation, and DNA repair. In rapidly proliferating cancer cells, CMPK1 functions as an essential enzyme in the pyrimidine biosynthetic pathway by catalyzing the phosphorylation of UMP and CMP to generate their diphosphate forms, thereby contributing to the maintenance of the nucleotide pool necessary for DNA/RNA synthesis and repair processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In PTEN‐null tumors with hyperactive AKT signaling, CMPK1 operates in concert with ENTPD5 and adenylate kinase‐1 to form an ATP hydrolysis cycle that drives a compensatory increase in aerobic glycolysis (the Warburg effect), underscoring its importance in cancer cell metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Moreover, CMPK1 has been implicated as a downstream target of the 4EBP1/eIF4E cascade in hepatocarcinogenesis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and its overexpression in ovarian and triple‐negative breast cancers appears to promote cell proliferation, migration, invasion, and altered cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Genetic polymorphisms in CMPK1 have also been shown to influence patient outcomes in gemcitabine‐based therapies for lung and pancreatic cancers, highlighting its role in drug activation and pharmacodynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, CMPK1 contributes to genomic stability by transiently localizing to sites of DNA damage—associating with repair factors such as Tip60—to facilitate localized dNTP synthesis for efficient DNA repair."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Unexpectedly, CMPK1 has been identified at the surface of vacuoles in intracellular bacteria, where it serves as a guanine nucleotide–independent and Rab10-specific ligand, revealing its potential involvement in host–pathogen interactions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Finally, genome-wide association studies have identified CMPK1 as one of the novel candidate genes influencing corneal curvature, suggesting that its functions may extend to ocular physiology"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and recent work linking miR-3613-3p to CMPK1 implicates the enzyme in the interferon-mediated antiviral response in chronic hepatitis B."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jieh-Yuan Liou, Ginger E Dutschman, Wing Lam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of human UMP/CMP kinase and its phosphorylation of D- and L-form deoxycytidine analogue monophosphates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2002)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11912132"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11912132"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rong Hu, Wing Lam, Chih-Hung Hsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UMP/CMPK is not the critical enzyme in the metabolism of pyrimidine ribonucleotide and activation of deoxycytidine analogs in human RKO cells."}]}, {"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.0019490"}], "href": "https://doi.org/10.1371/journal.pone.0019490"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21559290"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21559290"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Min Fang, Zhirong Shen, Song Huang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ER UDPase ENTPD5 promotes protein N-glycosylation, the Warburg effect, and proliferation in the PTEN pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cell.2010.10.010"}], "href": "https://doi.org/10.1016/j.cell.2010.10.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21074248"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21074248"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Chunmei Wang, Antonio Cigliano, Lijie Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "4EBP1/eIF4E and p70S6K/RPS6 axes play critical and distinct roles in hepatocarcinogenesis driven by AKT and N-Ras proto-oncogenes in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.27396"}], "href": "https://doi.org/10.1002/hep.27396"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25145583"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25145583"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Daibing Zhou, Lingyun Zhang, Wenwen Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytidine monophosphate kinase is inhibited by the TGF-β signalling pathway through the upregulation of miR-130b-3p in human epithelial ovarian cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2017.04.009"}], "href": "https://doi.org/10.1016/j.cellsig.2017.04.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28414100"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28414100"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Ning Qing Liu, Tommaso De Marchi, Annemieke Timmermans, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Prognostic significance of nuclear expression of UMP-CMP kinase in triple negative breast cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep32027"}], "href": "https://doi.org/10.1038/srep32027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27558661"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27558661"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Jeong-Seon Ryu, Eun-Soon Shin, Hae-Seong Nam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential effect of polymorphisms of CMPK1 and RRM1 on survival in advanced non-small cell lung cancer patients treated with gemcitabine or taxane/cisplatinum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thorac Oncol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/JTO.0b013e3182208e26"}], "href": "https://doi.org/10.1097/JTO.0b013e3182208e26"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21642870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21642870"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hye In Woo, Ka-Kyung Kim, Hangseok Choi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Effect of genetic polymorphisms on therapeutic response and clinical outcomes in pancreatic cancer patients treated with gemcitabine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacogenomics (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2217/pgs.12.82"}], "href": "https://doi.org/10.2217/pgs.12.82"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22838950"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22838950"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Ning Tsao, Ming-Hsiang Lee, Wei Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The contribution of CMP kinase to the efficiency of DNA repair."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/15384101.2014.987618"}], "href": "https://doi.org/10.4161/15384101.2014.987618"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25659034"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25659034"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Hilary K Truchan, Lauren VieBrock, Chelsea L Cockburn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Anaplasma phagocytophilum Rab10-dependent parasitism of the trans-Golgi network is critical for completion of the infection cycle."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Microbiol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cmi.12500"}], "href": "https://doi.org/10.1111/cmi.12500"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26289115"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26289115"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Qiao Fan, Alfred Pozarickij, Nicholas Y Q Tan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Commun Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s42003-020-0802-y"}], "href": "https://doi.org/10.1038/s42003-020-0802-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32193507"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32193507"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yanping Zhao, Yaping Yu, Lei Ye "}, {"type": "b", "children": [{"type": "t", "text": "MiR-3613-3p impairs IFN-induced immune response by targeting CMPK1 in chronic hepatitis B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Infect Genet Evol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.meegid.2019.103919"}], "href": "https://doi.org/10.1016/j.meegid.2019.103919"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31201869"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31201869"}]}]}]}