{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cyclin‐dependent kinase–like 1 (CDKL1) has emerged as a multifaceted serine/threonine kinase with important roles in cell proliferation, survival, and differentiation. In several human cancers—including gastric, breast, colon, oral squamous cell carcinoma, neuroblastoma, and melanoma—CDKL1 is frequently overexpressed, where its activity promotes cell cycle progression and tumor cell growth while inhibiting apoptosis. For example, in gastric and breast cancer studies, elevated CDKL1 levels were correlated with increased proliferation and reduced apoptotic responses, and its inhibition resulted in G0/G1 cell cycle arrest and enhanced apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In colon cancer, the transcription factor Egr‑1 directly regulates CDKL1, thereby influencing cell migration and invasion"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ", whereas in oral squamous cell carcinoma, CDKL1 overexpression was shown to decrease chemosensitivity and sustain robust cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Complementary findings in neuroblastoma and melanoma also demonstrated that knockdown of CDKL1 elicited cell cycle arrest, reduced colony formation, and induced apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " At the post‐transcriptional level, a regulatory axis involving noncoding RNA (circRACGAP1/miR‑144‑5p) was found to modulate CDKL1 expression, thereby impacting non–small cell lung cancer cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond oncogenesis, studies in model organisms have broadened our understanding of CDKL1 function. In the nematode Caenorhabditis elegans, the ortholog CDKL‑1 governs the length of a specific ciliary subdomain by modulating intraflagellar transport motor distribution"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", while in zebrafish, cdkl1 is critical for proper brain and eye development, with loss-of-function experiments leading to conspicuous neural and morphological abnormalities."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Structural studies have further revealed that CDKL1 belongs to an evolutionarily divergent kinase family distinct from canonical cyclin-dependent kinases and mitogen-activated protein kinases, a divergence that is associated with unique substrate recognition and regulatory features."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, emerging evidence suggests that CDKL1 may play roles in nonmalignant contexts. A study of neurodegeneration linked CDKL1-related sequence motifs with altered disease phenotypes"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", and investigations in an epididymitis model reported reduced CDKL1 levels in association with inflammatory tissue responses."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Furthermore, autoantibody profiling in narcolepsy has uncovered peptides from CDKL1 that share homology with vaccine antigens, hinting at possible immunogenic aspects of the kinase."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore CDKL1 as a critical regulator of cell growth and survival in cancer, a modulator of developmental and ciliary functions in model organisms, and a potential biomarker and therapeutic target across diverse pathological settings.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wei Sun, Li Yao, Benchun Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A role for Cdkl1 in the development of gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Oncol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3109/0284186X.2012.665611"}], "href": "https://doi.org/10.3109/0284186X.2012.665611"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22369697"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22369697"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Li Tang, Yanfang Gao, Feng Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evaluation of cyclin-dependent kinase-like 1 expression in breast cancer tissues and its regulation in cancer cell growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Biother Radiopharm (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/cbr.2012.1198"}], "href": "https://doi.org/10.1089/cbr.2012.1198"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22804458"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22804458"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Shanshan Shao, Man Ju, Jiayun Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Egr‑1 inhibits colon cancer cell proliferation, migration and invasion via regulating CDKL1 at the transcriptional level."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2021.8120"}], "href": "https://doi.org/10.3892/or.2021.8120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34165179"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34165179"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Keyi Li, Zhen Meng, Licheng Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDKL1 promotes the chemoresistance of human oral squamous cell carcinoma cells to hydroxycamptothecin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Probes (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.mcp.2019.02.004"}], "href": "https://doi.org/10.1016/j.mcp.2019.02.004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30802495"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30802495"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Weiyi Li, Jing Cao, Jian Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Downregulation of CDKL1 suppresses neuroblastoma cell proliferation, migration and invasion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol Lett (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s11658-019-0139-z"}], "href": "https://doi.org/10.1186/s11658-019-0139-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30891073"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30891073"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Zhiqi Song, Jingrong Lin, Zhe Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RNAi-mediated downregulation of CDKL1 inhibits growth and colony-formation ability, promotes apoptosis of human melanoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dermatol Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jdermsci.2015.03.020"}], "href": "https://doi.org/10.1016/j.jdermsci.2015.03.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25920913"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25920913"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Min Lu, Hui Xiong, Zhen-Kun Xia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "circRACGAP1 promotes non-small cell lung cancer proliferation by regulating miR-144-5p/CDKL1 signaling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Gene Ther (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41417-020-00209-0"}], "href": "https://doi.org/10.1038/s41417-020-00209-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32778770"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32778770"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Kwangjin Park, Chunmei Li, Sofia Tsiropoulou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDKL kinase regulates the length of the ciliary proximal segment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2021.03.068"}], "href": "https://doi.org/10.1016/j.cub.2021.03.068"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33857430"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33857430"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Li-Sung Hsu, Cyong-Jhih Liang, Chen-Yuan Tseng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Zebrafish cyclin-dependent protein kinase-like 1 (zcdkl1): identification and functional characterization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms12063606"}], "href": "https://doi.org/10.3390/ijms12063606"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21747697"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21747697"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Peter Canning, Kwangjin Park, João Gonçalves, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CDKL Family Kinases Have Evolved Distinct Structural Features and Ciliary Function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2017.12.083"}], "href": "https://doi.org/10.1016/j.celrep.2017.12.083"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29420175"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29420175"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Dennis W Dickson, Matthew C Baker, Jazmyne L Jackson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extensive transcriptomic study emphasizes importance of vesicular transport in C9orf72 expansion carriers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40478-019-0797-0"}], "href": "https://doi.org/10.1186/s40478-019-0797-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31594549"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31594549"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Xin Song, Nan-He Lin, You-Lin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Comprehensive transcriptome analysis based on RNA sequencing identifies critical genes for lipopolysaccharide-induced epididymitis in a rat model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Asian J Androl (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4103/aja.aja_21_19"}], "href": "https://doi.org/10.4103/aja.aja_21_19"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31044753"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31044753"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Anna Häggmark-Månberg, Arash Zandian, Björn Forsström, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Autoantibody targets in vaccine-associated narcolepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Autoimmunity (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/08916934.2016.1183655"}], "href": "https://doi.org/10.1080/08916934.2016.1183655"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27206786"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27206786"}]}]}]}