{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe SLC31A1 gene encodes copper transporter 1 (CTR1), a small, highly conserved, trimeric membrane protein that plays an essential role in high‐affinity copper uptake in eukaryotic cells. CTR1 forms a pore across the plasma membrane, and its topology and structure—revealed by biochemical studies and electron crystallography—highlight the importance of extracellular methionine clusters and conserved MXXXM motifs in coordinating copper ions during translocation. These structural features are critical not only for ensuring proper copper homeostasis but also for supplying copper to key intracellular enzymes involved in processes such as respiration, oxidative stress protection, iron metabolism, and hormone synthesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its central role in copper homeostasis, CTR1 also mediates the uptake of platinum‐based chemotherapeutic agents such as cisplatin. In response to elevated extracellular copper, CTR1 is internalized via clathrin‐dependent endocytosis—a regulatory mechanism that not only protects cells from copper toxicity but also modulates the influx of platinum drugs. Alterations in CTR1 expression, its trafficking dynamics, and even genetic polymorphisms have been closely linked to variations in cisplatin accumulation, chemoresistance, and clinical outcomes in several cancer types. Moreover, CTR1 has been implicated in the uptake of other metal ions and its function is influenced by interactions with cellular reductants, chaperones, and regulatory molecules (including microRNAs and transcription factors), making it an emerging therapeutic target and potential biomarker in precision oncology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "37"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sergi Puig, Jaekwon Lee, Miranda Lau, et al. 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