{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe TPTEP2‐CSNK1E gene product appears to drive pathogenic phosphorylation events that promote neurodegenerative proteinopathies. In a Drosophila model of TDP‐43 proteinopathy, enhancement of toxicity by overexpressed TDP‐43(Q331K) was observed upon coexpression with doubletime (the fly homolog of casein kinase Iε, encoded by CSNK1E), which increased phosphorylation at the disease‐associated Ser409/410 epitope and promoted the assembly of high–molecular weight toxic oligomers. These findings support a critical role for the CSNK1E portion of TPTEP2‐CSNK1E in modulating TDP‐43 phosphorylation and toxicity in vivo."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn contrast to the post–translational regulatory role of CSNK1E in neurodegeneration, several studies have characterized members of the BTB–C2H2 zinc finger family—particularly ZNF131—as pivotal transcriptional regulators in diverse cellular contexts. Detailed analyses have revealed that ZNF131 exists as alternatively spliced isoforms expressed predominantly in the developing and adult central nervous system, where it influences gene transcription through both activation and repression mechanisms."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "2", "end_ref": "4"}]}, {"type": "t", "text": " \n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond neural development, ZNF131 has been implicated in the regulation of cell cycle progression, immunoglobulin gene rearrangement during lymphocyte development, and even oncogenic signaling in hepatocellular carcinoma via transcriptional control of downstream effectors such as PAIP1 and Cyclin D1."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": " This collection of studies underscores that while transcription factors like ZNF131 regulate gene expression programs essential for cellular differentiation and proliferation, the kinase activity contributed by CSNK1E within TPTEP2‐CSNK1E exerts a distinct influence by modulating protein phosphorylation events that may trigger or exacerbate neurodegenerative cascades.\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Darshana K Choksi, Bidisha Roy, Shreyasi Chatterjee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TDP-43 Phosphorylation by casein kinase Iε promotes oligomerization and enhances toxicity in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt498"}], "href": "https://doi.org/10.1093/hmg/ddt498"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24105464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24105464"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "R Trappe, P Buddenberg, J Uedelhoven, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The murine BTB/POZ zinc finger gene Znf131: predominant expression in the developing central nervous system, in adult brain, testis, and thymus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0006-291x(02)00850-1"}], "href": "https://doi.org/10.1016/s0006-291x(02"}, {"type": "t", "text": "00850-1) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12163020"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12163020"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nickett S Donaldson, Yasmin Daniel, Kevin F Kelly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear trafficking of the POZ-ZF protein Znf131."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2006.12.005"}], "href": "https://doi.org/10.1016/j.bbamcr.2006.12.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17306895"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17306895"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Nickett S Donaldson, Curtis L Nordgaard, Christina C Pierre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kaiso regulates Znf131-mediated transcriptional activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2010.03.011"}], "href": "https://doi.org/10.1016/j.yexcr.2010.03.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20303951"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20303951"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tomohiro Iguchi, Kazuhisa Aoki, Tomokatsu Ikawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "BTB-ZF Protein Znf131 Regulates Cell Growth of Developing and Mature T Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1500602"}], "href": "https://doi.org/10.4049/jimmunol.1500602"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26136427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26136427"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shaiya C Robinson, Nickett S Donaldson-Kabwe, Anna Dvorkin-Gheva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The POZ-ZF transcription factor Znf131 is implicated as a regulator of Kaiso-mediated biological processes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2017.09.007"}], "href": "https://doi.org/10.1016/j.bbrc.2017.09.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28882591"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28882591"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Tomohiro Iguchi, Emako Miyauchi, Sumiko Watanabe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A BTB-ZF protein, ZNF131, is required for early B cell development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2018.05.044"}], "href": "https://doi.org/10.1016/j.bbrc.2018.05.044"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29750959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29750959"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Görkem Garipler, Congyi Lu, Alexis Morrissey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The BTB transcription factors ZBTB11 and ZFP131 maintain pluripotency by repressing pro-differentiation genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2022.110524"}], "href": "https://doi.org/10.1016/j.celrep.2022.110524"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35294876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35294876"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Guozhi Yin, Siying Jia, Youju Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "YAP1-activated ZNF131 promotes hepatocellular carcinoma cell proliferation through transcriptional regulation of PAIP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Biochem Biophys (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.abb.2024.109921"}], "href": "https://doi.org/10.1016/j.abb.2024.109921"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38341068"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38341068"}]}]}]}