{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlthough none of the provided abstracts explicitly mention SNORD115‐23, the collection of studies offers a rich insight into the multifaceted functions of USP4, a deubiquitinating enzyme whose activities may serve as a conceptual parallel when considering regulatory RNAs. In several investigations, USP4 is shown to dynamically shuttle between the nucleus and cytoplasm to precisely modulate key signaling cascades. For example, USP4 deubiquitinates substrates that control proliferative and survival pathways, including the stabilization of ARF‐BP1 to downregulate p53 levels and the deubiquitination of TRAF6 to temper TLR/IL‐1R–mediated innate immune responses, while also interacting with the transforming growth factor–β (TGF‐β) receptor I at the plasma membrane to sustain TGF‐β signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOther studies extend the biological scope of USP4 activity to the regulation of tissue homeostasis and repair. In the liver, USP4 is implicated in fibrogenic processes through its role in maintaining TGF‐β receptor I levels—as part of an H19/miR‐148a/USP4 axis—and in modulating inflammatory and stress responses during nonalcoholic fatty liver disease and hepatic ischemia/reperfusion injury via regulation of TAK1/JNK signaling. Moreover, USP4 participates in renal water homeostasis by deubiquitinating aquaporin 2, and its inhibition has been shown to reduce pathological scarring through modulation of TGF‐β/Smad signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in stress and tissue homeostasis, USP4 influences cell differentiation and disease progression. In the context of myogenesis and immune regulation, USP4 acts as a modulator of myogenic regulatory factors and has been implicated in dampening inflammatory responses in conditions such as asthma, where it regulates T regulatory and Th17 cell balance. Furthermore, stabilization of USP4 by FBXO3 in breast cancer cells links its deubiquitinating activity to the promotion of metastasis via Twist1 protein stabilization, while its regulation of ribosome biogenesis and protein synthesis is critical for hematopoietic stem cell regeneration and leukemia progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Tatiana A Soboleva, David A Jans, Melanie Johnson-Saliba, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nuclear-cytoplasmic shuttling of the oncogenic mouse UNP/USP4 deubiquitylating enzyme."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M401394200"}], "href": "https://doi.org/10.1074/jbc.M401394200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15494318"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15494318"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xinna Zhang, Franklin G Berger, Jianhua Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "USP4 inhibits p53 through deubiquitinating and stabilizing ARF-BP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2011.125"}], "href": "https://doi.org/10.1038/emboj.2011.125"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21522127"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21522127"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "FangFang Zhou, Xiaofei Zhang, Hans van Dam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin-specific protease 4 mitigates Toll-like/interleukin-1 receptor signaling and regulates innate immune activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.328187"}], "href": "https://doi.org/10.1074/jbc.M111.328187"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22262844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22262844"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Long Zhang, FangFang Zhou, Yvette Drabsch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "USP4 is regulated by AKT phosphorylation and directly deubiquitylates TGF-β type I receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2522"}], "href": "https://doi.org/10.1038/ncb2522"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22706160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22706160"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sun-Il Yun, Kyeong Kyu Kim "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin-specific protease 4 (USP4) suppresses myoblast differentiation by down regulating MyoD activity in a catalytic-independent manner."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2017.03.008"}], "href": "https://doi.org/10.1016/j.cellsig.2017.03.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28336234"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28336234"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Fangfang Zhou, Feng Xie, Ke Jin, et al. 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