{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent studies have revealed that the RFPL3 gene—a member of the ret finger protein‐like family—plays a critical role in brain development. In primates, gene duplication and neofunctionalization events in the RFPL1,2,3 cluster have led to markedly increased transcript levels in the developing neocortex. Such evolutionary innovations suggest that RFPL3 may contribute to the increased size and complex organization of the primate neocortex, likely through its regulation by factors such as Pax6."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn a distinct context, RFPL3 has been identified as a novel cellular factor that stimulates retroviral integration. Functional screening using a wheat germ cell‐free protein library revealed that RFPL3 enhances HIV‐1 preintegration complex activity in vitro. The stimulatory effect appears to depend on its N‐terminal RING domain, suggesting that RFPL3 can promote viral DNA insertion into the host genome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, in lung cancer cells RFPL3 functions as a transcriptional activator of the human telomerase reverse transcriptase (hTERT) promoter. RFPL3 binds directly to the hTERT promoter and, through interaction and acetylation mediated by CBP, upregulates hTERT expression and telomerase activity, thereby promoting tumor cell growth and correlating with poor prognosis and metastasis. Additional evidence indicates that RFPL3 overexpression is linked to activation of the EGFR–MEK signaling cascade, which further elevates the expression of hTERT and related proliferative proteins."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jérôme Bonnefont, Sergey I Nikolaev, Anselme L Perrier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Evolutionary forces shape the human RFPL1,2,3 genes toward a role in neocortex development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2008.07.007"}], "href": "https://doi.org/10.1016/j.ajhg.2008.07.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18656177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18656177"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Beng Hui Tan, Yasutsugu Suzuki, Hirotaka Takahashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of RFPL3 protein as a novel E3 ubiquitin ligase modulating the integration activity of human immunodeficiency virus, type 1 preintegration complex using a microtiter plate-based assay."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.561662"}], "href": "https://doi.org/10.1074/jbc.M114.561662"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25107902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25107902"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Wangbing Chen, Jianjun Lu, Yu Qin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ret finger protein-like 3 promotes tumor cell growth by activating telomerase reverse transcriptase expression in human lung cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.2557"}], "href": "https://doi.org/10.18632/oncotarget.2557"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25481043"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25481043"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yu Qin, Wangbing Chen, Yao Xiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RFPL3 and CBP synergistically upregulate hTERT activity and promote lung cancer growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.4825"}], "href": "https://doi.org/10.18632/oncotarget.4825"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26318425"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26318425"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chuan Lin, Yu Qin, Hua Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EGF upregulates RFPL3 and hTERT via the MEK signaling pathway in non‑small cell lung cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2018.6417"}], "href": "https://doi.org/10.3892/or.2018.6417"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29749533"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29749533"}]}]}]}