{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPQLC2, a member of the PQ‐loop transporter family and representative of SLC66A1 function, acts as a lysosomal/vacuolar exporter of cationic amino acids. It mediates the efflux of amino acids such as arginine, lysine, and related metabolites—and importantly, it transports a lysine‐like mixed disulfide that forms during cysteamine therapy for cystinosis. This function is conserved from yeast (Ypq1–3) to mammals, suggesting that small-molecule export is a fundamental attribute of this protein family."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n \nDis primis, PQLC2 also functions as a transceptor: its conformational states during substrate transport regulate the exposure of a binding site that, in turn, recruits a regulatory protein complex composed of WDR41, SMCR8, and C9orf72 to the lysosomal surface. This interaction links amino acid availability to the modulation of lysosome function, emphasizing its dual role as both transporter and sensor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n \nIn addition to maintaining intracellular amino acid homeostasis, upregulation of PQLC2 has been implicated in tumor progression. Overexpression in gastric cancer cells promotes cell proliferation, anchorage-independent growth, and tumor formation through activation of the MEK/ERK1/2 and PI3K/AKT signaling pathways, whereas knockdown leads to growth arrest and cell death. These findings underscore its potential as a target for therapeutic intervention in cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Adrien Jézégou, Elisa Llinares, Christine Anne, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter underlying the action of cysteamine in cystinosis therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1211198109"}], "href": "https://doi.org/10.1073/pnas.1211198109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23169667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23169667"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Gabriel Talaia, Joseph Amick, Shawn M Ferguson "}, {"type": "b", "children": [{"type": "t", "text": "Receptor-like role for PQLC2 amino acid transporter in the lysosomal sensing of cationic amino acids."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2014941118"}], "href": "https://doi.org/10.1073/pnas.2014941118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33597295"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33597295"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yun-Ji Jeung, Kyeong Lee, Hyo Jin Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cationic amino acid transporter PQLC2 is a potential therapeutic target in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.13966"}], "href": "https://doi.org/10.1111/cas.13966"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30729615"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30729615"}]}]}]}