{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTCFL5’s molecular functions emerge in part from studies of its alternatively spliced isoform, CHA, which was characterized as a basic helix‐loop‐helix transcription factor. In this context, CHA forms heterodimers with proteins such as USF1 and cannot bind DNA on its own; rather, it modulates transcription by negatively regulating USF‐dependent gene expression (e.g., CD2) in T cells. This activity suggests that at least one TCFL5 isoform plays a role in fine‐tuning transcriptional programs during immune cell quiescence and activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the setting of human spermatogenesis, TCFL5 expression is tightly regulated and cell stage–specific. Studies demonstrate that TCFL5 is expressed in primary spermatocytes engaged in the first meiotic division, in secondary spermatocytes, and in round spermatids. Its absence in certain testicular germ cell neoplasms further supports a role for TCFL5 in promoting appropriate progression of germ cell differentiation during spermatogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn colorectal cancer, TCFL5 is expressed as four alternative transcripts whose functions diverge markedly. Notably, the TCFL5_E8 and CHA isoforms exert opposite effects on tumor biology: while TCFL5_E8 attenuates proliferation, spheroid formation, and even in vivo tumor growth, the CHA isoform promotes these pro-tumoral properties. Both isoforms directly bind to the promoters of pluripotency-associated genes (SOX2 and KLF4) but regulate them in contrasting manners. These findings underscore an isoform-specific regulatory role for TCFL5 in tumor development and progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, emerging evidence links TCFL5 to chemotherapy resistance mechanisms in hematologic malignancies, notably diffuse large B-cell lymphoma and childhood acute lymphoblastic leukemia. Although the precise molecular underpinnings remain to be fully elucidated, such observations suggest that TCFL5 may contribute to the drug-resistant phenotype observed in these cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Clara I Rodríguez, Núria Gironès, Manuel Fresno "}, {"type": "b", "children": [{"type": "t", "text": "Cha, a basic helix-loop-helix transcription factor involved in the regulation of upstream stimulatory factor activity."}]}, {"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.M300053200"}], "href": "https://doi.org/10.1074/jbc.M300053200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12923186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12923186"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Lawrence M Roth, Michal Michal, Michael Michal, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Protein expression of the transcription factors DMRT1, TCLF5, and OCT4 in selected germ cell neoplasms of the testis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Pathol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.humpath.2018.07.019"}], "href": "https://doi.org/10.1016/j.humpath.2018.07.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30067948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30067948"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Javier Galán-Martínez, Konstantinos Stamatakis, Inés Sánchez-Gómez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Isoform-specific effects of transcription factor TCFL5 on the pluripotency-related genes SOX2 and KLF4 in colorectal cancer development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Oncol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1878-0261.13085"}], "href": "https://doi.org/10.1002/1878-0261.13085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34623757"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34623757"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xueying Lu, Quan'e Zhang, Yandong Xie "}, {"type": "b", "children": [{"type": "t", "text": "TCFL5 knockdown sensitizes DLBCL to doxorubicin treatment via regulation of GPX4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2023.110831"}], "href": "https://doi.org/10.1016/j.cellsig.2023.110831"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37516394"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37516394"}]}]}]}