{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTSAP6, also known as STEAP3, is a p53‐responsive multi‐transmembrane protein that operates at the interface of cell stress responses and intercellular communication. It has been shown to regulate exosome formation and protein secretion—processes that not only influence apoptosis but also aid in the removal of damaged cellular components. In p53‐induced contexts, TSAP6 enhances apoptotic pathways through interactions with proapoptotic proteins and cell‐cycle regulators, helping to ensure proper cell-cycle progression and tumor suppression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in programmed cell death and exosome secretion, TSAP6/STEAP3 is central to iron metabolism. Functioning as a ferrireductase, it is vital for the uptake of iron in developing erythroblasts, thereby supporting normal red blood cell maturation. Mutational analyses and genetic screens have revealed that alterations in TSAP6/STEAP3—either by point mutations or decreased allelic expression—result in microcytic and hypochromic anemia owing to impaired erythropoiesis. Moreover, its involvement in the regulation of iron homeostasis extends to macrophage populations, linking iron metabolism with inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging evidence also implicates TSAP6/STEAP3 in the modulation of tissue remodeling and injury responses. In cardiovascular tissues, STEAP3 acts as a negative regulator of pathological cardiac hypertrophy by dampening Rac1‐dependent signaling cascades, thereby offering cardioprotection against stress-induced remodeling. Similarly, alterations in its expression have been associated with hepatic ischemia-reperfusion injury, suggesting a broader role in mediating inflammatory and apoptotic processes in different organ systems."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Brent J Passer, Vanessa Nancy-Portebois, Nathalie Amzallag, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0530298100"}], "href": "https://doi.org/10.1073/pnas.0530298100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12606722"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12606722"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "A Lespagnol, D Duflaut, C Beekman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Exosome secretion, including the DNA damage-induced p53-dependent secretory pathway, is severely compromised in TSAP6/Steap3-null mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cdd.2008.104"}], "href": "https://doi.org/10.1038/cdd.2008.104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18617898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18617898"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Teresa Lambe, Robert J Simpson, Sara Dawson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a Steap3 endosomal targeting motif essential for normal iron metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-11-120402"}], "href": "https://doi.org/10.1182/blood-2007-11-120402"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18955558"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18955558"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Bernard Grandchamp, Gilles Hetet, Caroline Kannengiesser, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel type of congenital hypochromic anemia associated with a nonsense mutation in the STEAP3/TSAP6 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-01-329011"}], "href": "https://doi.org/10.1182/blood-2011-01-329011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22031863"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22031863"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Fan Zhang, Yunlong Tao, Zhuzhen Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metalloreductase Steap3 coordinates the regulation of iron homeostasis and inflammatory responses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Haematologica (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3324/haematol.2012.063974"}], "href": "https://doi.org/10.3324/haematol.2012.063974"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22689674"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22689674"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lionel Blanc, Julien Papoin, Gargi Debnath, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Abnormal erythroid maturation leads to microcytic anemia in the TSAP6/Steap3 null mouse model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hematol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajh.23920"}], "href": "https://doi.org/10.1002/ajh.23920"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25515317"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25515317"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Wen-Zhi Guo, Hong-Bo Fang, Sheng-Li Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Six-Transmembrane Epithelial Antigen of the Prostate 3 Deficiency in Hepatocytes Protects the Liver Against Ischemia-Reperfusion Injury by Suppressing Transforming Growth Factor-β-Activated Kinase 1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.30882"}], "href": "https://doi.org/10.1002/hep.30882"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31393024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31393024"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Peng-Long Li, Hui Liu, Guo-Peng Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "STEAP3 (Six-Transmembrane Epithelial Antigen of Prostate 3) Inhibits Pathological Cardiac Hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hypertension (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/HYPERTENSIONAHA.120.14752"}], "href": "https://doi.org/10.1161/HYPERTENSIONAHA.120.14752"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32862709"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32862709"}]}]}]}