{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ALKBH4 is a multifunctional Fe(II)/2‐oxoglutarate–dependent dioxygenase that contributes to the regulation of both epigenetic and cytoskeletal processes. Initial studies indicate that ALKBH4 can remove methyl groups from nucleic acid bases—for example, participating in the reversal of adenine N6 methylation in DNA, a modification linked to transcriptional silencing and Polycomb function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, ALKBH4 is well established as an actin demethylase that specifically targets monomethylated lysine‐84 on actin. This activity is crucial for promoting the interaction between actin and non‐muscle myosin II, thereby ensuring proper actomyosin dynamics required for cytokinesis, cell migration, and embryonic development"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ";"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in modulating the cytoskeleton, ALKBH4 has been shown to interact with chromatin‐associated factors, suggesting a potential influence on gene expression and chromatin state, although global transcriptional changes upon ALKBH4 over‐expression appear modest."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Biophysical analyses further confirm that ALKBH4 exhibits active decarboxylase activity and possesses a unique cysteine‐rich motif, hinting at additional, yet-to-be–defined, regulatory functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Dysregulation of ALKBH4 has been observed in various human cancers. In some contexts, such as non–small‐cell lung cancer, elevated ALKBH4 expression correlates with increased cellular proliferation"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": ", whereas in colorectal cancer its down‐regulation is associated with enhanced metastatic potential, possibly through effects on histone modifications involving partners like WDR5."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Similar context‐dependent associations have been reported in hepatocellular carcinoma, further underscoring the importance of ALKBH4 as a potential prognostic marker and therapeutic target."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies establish ALKBH4 as a versatile enzyme that integrates epigenetic regulation with cytoskeletal dynamics, thereby playing critical roles in normal development—including spermatogenesis and embryonic morphogenesis—and in the pathogenesis of cancer.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Soo-Mi Kweon, Yibu Chen, Eugene Moon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An Adversarial DNA N"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "6"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "-Methyladenine-Sensor Network Preserves Polycomb Silencing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molcel.2019.03.018"}], "href": "https://doi.org/10.1016/j.molcel.2019.03.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30982744"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30982744"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Ming-Ming Li, Anja Nilsen, Yue Shi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ALKBH4-dependent demethylation of actin regulates actomyosin dynamics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms2863"}], "href": "https://doi.org/10.1038/ncomms2863"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23673617"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23673617"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Anja Nilsen, Markus Fusser, Gareth Greggains, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ALKBH4 depletion in mice leads to spermatogenic defects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0105113"}], "href": "https://doi.org/10.1371/journal.pone.0105113"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25153837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25153837"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qingrui Sun, Xingfeng Liu, Bo Gong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alkbh4 and Atrn Act Maternally to Regulate Zebrafish Epiboly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Biol Sci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7150/ijbs.19203"}], "href": "https://doi.org/10.7150/ijbs.19203"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28924386"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28924386"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Linn G Bjørnstad, Trine J Meza, Marit Otterlei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human ALKBH4 interacts with proteins associated with transcription."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0049045"}], "href": "https://doi.org/10.1371/journal.pone.0049045"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23145062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23145062"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Linn G Bjørnstad, Giorgio Zoppellaro, Ane B Tomter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spectroscopic and magnetic studies of wild-type and mutant forms of the Fe(II)- and 2-oxoglutarate-dependent decarboxylase ALKBH4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20101667"}], "href": "https://doi.org/10.1042/BJ20101667"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21166655"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21166655"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Kentaro Jingushi, Masaya Aoki, Kazuhiro Ueda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ALKBH4 promotes tumourigenesis with a poor prognosis in non-small-cell lung cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-87763-1"}], "href": "https://doi.org/10.1038/s41598-021-87763-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33883577"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33883577"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Chaoqin Shen, Tingting Yan, Tianying Tong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ALKBH4 Functions as a Suppressor of Colorectal Cancer Metastasis via Competitively Binding to WDR5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Cell Dev Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fcell.2020.00293"}], "href": "https://doi.org/10.3389/fcell.2020.00293"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32478065"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32478065"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Bi Peng, Yuanliang Yan, Zhijie Xu "}, {"type": "b", "children": [{"type": "t", "text": "The bioinformatics and experimental analysis of AlkB family for prognosis and immune cell infiltration in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PeerJ (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7717/peerj.12123"}], "href": "https://doi.org/10.7717/peerj.12123"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34557360"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34557360"}]}]}]}