{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe ribosomal protein large P1 (RPLP1) plays a critical regulatory role in promoting cell proliferation and transformation. Elevated expression of RPLP1 has been shown to stimulate the activation of the E2F1 promoter and upregulate cyclin E, thereby bypassing replicative senescence and contributing to oncogenic transformation when co‐expressed with mutant ras. These findings suggest that RPLP1 overexpression is not merely a consequence of increased cellular proliferation, but actively drives it, as evidenced by its enhanced expression in human colon cancer specimens."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "The essential nature of RPLP1 is further underscored by its role in development and tissue homeostasis. Disruption of Rplp1 in mouse models leads to systemic developmental abnormalities, male infertility, and early postnatal lethality. In the central nervous system, Rplp1 deletion results in proliferation arrest and apoptosis in the neocortex, along with dysregulation of critical cell cycle regulators such as cyclin A, cyclin E, p21^CIP1, p27^KIP1, and p53. Notably, the absence of RPLP1 alters the expression of specific proteins involved in protein folding and the unfolded protein response without markedly affecting global protein synthesis, pointing to its role in translation “fine-tuning.”."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "In addition, increased RPLP1 expression is implicated in pathophysiological conditions beyond cancer and development. In endometriosis, ectopic lesions exhibit significantly higher levels of RPLP1 compared to eutopic endometrium, and experiments using a murine model have recapitulated this expression pattern. Moreover, knockdown studies in an endometriosis cell line indicate that RPLP1 is critical for cell survival. Although the underlying mechanisms governing protein translation in metabolic dysfunction-associated steatohepatitis remain to be fully elucidated, these observations suggest that RPLP1 contributes to cellular proliferation and survival in diverse pathological settings."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "A Artero-Castro, H Kondoh, P J Fernández-Marcos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rplp1 bypasses replicative senescence and contributes to transformation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2009.02.007"}], "href": "https://doi.org/10.1016/j.yexcr.2009.02.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19233166"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19233166"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Laura Perucho, Ana Artero-Castro, Sergi Guerrero, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RPLP1, a crucial ribosomal protein for embryonic development of the nervous system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0099956"}], "href": "https://doi.org/10.1371/journal.pone.0099956"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24959908"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24959908"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zahraa Alali, Amanda Graham, Kimberly Swan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "60S acidic ribosomal protein P1 (RPLP1) is elevated in human endometriotic tissue and in a murine model of endometriosis and is essential for endometriotic epithelial cell survival in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Hum Reprod (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/molehr/gaz065"}], "href": "https://doi.org/10.1093/molehr/gaz065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31899515"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31899515"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Madhulika Tripathi, Karine Gauthier, Reddemma Sandireddy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Esrra regulates Rplp1-mediated translation of lysosome proteins suppressed in metabolic dysfunction-associated steatohepatitis and reversed by alternate day fasting."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Metab (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molmet.2024.101997"}], "href": "https://doi.org/10.1016/j.molmet.2024.101997"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39032642"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39032642"}]}]}]}