{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUbiquitin‐specific protease 47 (USP47) has emerged as a critical regulator in multiple disease contexts. In chronic myelogenous leukemia (CML), USP47 facilitates DNA damage repair and sustains the proliferation of both tyrosine kinase inhibitor (TKI)–sensitive and –resistant cells by stabilizing factors such as the Y‐box binding protein 1. Its inhibition not only suppresses leukemic cell growth but also curtails the leukemic stem/progenitor cell pool, offering a promising strategy to overcome TKI resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the gastrointestinal tract, USP47 exerts an anti‐inflammatory effect. By removing K63‐linked polyubiquitin chains from TRAF6, it dampens NF‐κB signaling and thereby mitigates inflammatory responses in intestinal epithelial cells. Loss of USP47 leads to heightened proinflammatory cytokine production and more severe colitis, underscoring its role in protecting against inflammatory bowel disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nUSP47 also contributes to tissue regeneration and the cellular response to oxidative injury. In the liver, its function is linked to the regenerative proliferation of hepatocytes following injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In the skin, USP47 induction in response to oxidative stress regulates mitochondrial homeostasis by modulating the degradation of key proteins like nicotinamide nucleotide transhydrogenase (NNT). Deficiency of USP47 aggravates oxidative damage, as evidenced by increased reactive oxygen species accumulation and disrupted energy production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cellular stress and regenerative responses, USP47 influences the tumor microenvironment. In prostate cancer models, decreased USP47 expression is associated with slower tumor growth, due in part to elevated infiltration of immune cells—including cytotoxic T lymphocytes, neutrophils, macrophages, and natural killer cells—which results in enhanced antitumor immune responses. These findings position USP47 not only as a mediator of intrinsic tumor cell survival but also as an important modulator of the host immune response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hu Lei, Han-Zhang Xu, Hui-Zhuang Shan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting USP47 overcomes tyrosine kinase inhibitor resistance and eradicates leukemia stem/progenitor cells in chronic myelogenous leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-20259-0"}], "href": "https://doi.org/10.1038/s41467-020-20259-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33397955"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33397955"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hu Lei, Li Yang, Hanzhang Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin-specific protease 47 regulates intestinal inflammation through deubiquitination of TRAF6 in epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci China Life Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11427-021-2040-8"}], "href": "https://doi.org/10.1007/s11427-021-2040-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35235149"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35235149"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yuwen Zhu, Yan Guo, Hong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin specific peptidase 47 contributes to liver regeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Life Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.lfs.2023.121967"}], "href": "https://doi.org/10.1016/j.lfs.2023.121967"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37487274"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37487274"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaoqian Li, Kun Qian, Yuehua Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin-specific peptidase 47 (USP47) regulates cutaneous oxidative injury through nicotinamide nucleotide transhydrogenase (NNT)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Toxicol Appl Pharmacol (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.taap.2023.116734"}], "href": "https://doi.org/10.1016/j.taap.2023.116734"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37924851"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37924851"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Qian-Lan Wang, Shun-Yuan Lu, Dan-Dan Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "USP47 deficiency in mice modulates tumor infiltrating immune cells and enhances antitumor immune responses in prostate cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Immunol Immunother (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00262-024-03730-5"}], "href": "https://doi.org/10.1007/s00262-024-03730-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38832955"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38832955"}]}]}]}