{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRPL23 plays a pivotal role in the regulation of the p53 tumor suppressor pathway by directly binding to MDM2 and thereby inhibiting MDM2‐mediated ubiquitination and degradation of p53. Studies have demonstrated that RPL23, together with other ribosomal proteins (such as L5 and L11), forms complexes that stabilize and activate p53, particularly under stress conditions like low‐dose actinomycin D. This mechanistic insight has been exploited in gene therapy approaches where co‐expression of RPL23 with p53 enhanced antitumor responses in models of gastric and colorectal cancers, underscoring its therapeutic potential."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to modulating the p53 pathway, RPL23 also impacts cell cycle progression and apoptotic regulation. Altered expression levels of RPL23 affect the activity of the transcription factor Miz1, a key regulator of cell cycle inhibitors such as p15Ink4b and p21Cip1. Elevated RPL23 levels have been linked to reduced Miz1 activity—with concomitant upregulation of its functional antagonist c-Myc—which collectively diminish the induction of these inhibitors, leading to apoptotic resistance. This mechanistic alteration has been observed in patients with higher-risk myelodysplastic syndrome, where increased RPL23 expression correlates with decreased apoptosis, disease progression, and poorer responses to specific chemotherapeutic regimens."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, overexpression of RPL23 has been implicated in the development of multidrug resistance and in promoting oncogenic properties. In gastric cancer cells, enforced expression of RPL23 not only protects cells from drug-induced apoptosis by altering the balance of apoptotic proteins and enhancing detoxification systems (e.g., via increased glutathione S-transferase activity) but also in head and neck squamous cell carcinoma, where elevated RPL23 acts as a novel tumor antigen associated with enhanced proliferation, invasion, and even cellular transformation. These findings highlight RPL23’s dual potential as a biomarker for aggressive cancer phenotypes and as a target for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mu-Shui Dai, Hua Lu "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of MDM2-mediated p53 ubiquitination and degradation by ribosomal protein L5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M403722200"}], "href": "https://doi.org/10.1074/jbc.M403722200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15308643"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15308643"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mu-Shui Dai, Shelya X Zeng, Yetao Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ribosomal protein L23 activates p53 by inhibiting MDM2 function in response to ribosomal perturbation but not to translation inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.24.17.7654-7668.2004"}], "href": "https://doi.org/10.1128/MCB.24.17.7654-7668.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15314173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15314173"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Aiwen Jin, Koji Itahana, Kevin O'Keefe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Inhibition of HDM2 and activation of p53 by ribosomal protein L23."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.24.17.7669-7680.2004"}], "href": "https://doi.org/10.1128/MCB.24.17.7669-7680.2004"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15314174"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15314174"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ya-Fei Zhang, Bi-Cheng Zhang, An-Ran Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Co-transduction of ribosomal protein L23 enhances the therapeutic efficacy of adenoviral-mediated p53 gene transfer in human gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2013.2663"}], "href": "https://doi.org/10.3892/or.2013.2663"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23933826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23933826"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Henghu Fang, Jingbo Kang, Rui Du, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Growth inhibitory effect of adenovirus-mediated tissue-targeted expression of ribosomal protein L23 on human colorectal carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncol Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/or.2015.4026"}], "href": "https://doi.org/10.3892/or.2015.4026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26044651"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26044651"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Michael Wanzel, Annika C Russ, Daniela Kleine-Kohlbrecher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A ribosomal protein L23-nucleophosmin circuit coordinates Mizl function with cell growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb1764"}], "href": "https://doi.org/10.1038/ncb1764"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19160485"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19160485"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yuekun Qi, Xiao Li, Chunkang Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ribosomal protein L23 negatively regulates cellular apoptosis via the RPL23/Miz-1/c-Myc circuit in higher-risk myelodysplastic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-02403-x"}], "href": "https://doi.org/10.1038/s41598-017-02403-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28539603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28539603"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lingyun Wu, Xiao Li, Feng Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Over-expression of RPL23 in myelodysplastic syndromes is associated with apoptosis resistance of CD34+ cells and predicts poor prognosis and distinct response to CHG chemotherapy or decitabine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Hematol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00277-012-1486-2"}], "href": "https://doi.org/10.1007/s00277-012-1486-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22580751"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22580751"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yongquan Shi, Huihong Zhai, Xin Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ribosomal proteins S13 and L23 promote multidrug resistance in gastric cancer cells by suppressing drug-induced apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2004.02.009"}], "href": "https://doi.org/10.1016/j.yexcr.2004.02.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15149863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15149863"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "N Russo, X Wang, M Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel approach to biomarker discovery in head and neck cancer using an autoantibody signature."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2012.532"}], "href": "https://doi.org/10.1038/onc.2012.532"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23160375"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23160375"}]}]}]}