{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOTUD7B, also known as Cezanne (or Cezanne-1), is a deubiquitinating enzyme of the ovarian tumor (OTU) protease family that displays intrinsic specificity toward distinct polyubiquitin linkages. Structural and biochemical studies have demonstrated that OTUD7B preferentially disassembles Lys11‐linked ubiquitin chains, with structural analyses and ubiquitin binding assays revealing that its catalytic and N‐terminal ubiquitin-associated domains are essential for substrate recognition and activity. Furthermore, post‐translational modifications such as asparagine hydroxylation of its UBA-like domain can modulate its ability to interact with various ubiquitin chain types, thereby fine‐tuning its deubiquitinating function."}, {"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": "\nIn addition to its defined enzymatic specificity, OTUD7B functions as a critical regulator of inflammatory and receptor‐mediated signaling pathways. By deubiquitinating key signaling intermediates, OTUD7B attenuates NF‐κB activation downstream of tumor necrosis factor receptor stimulation, in part through removing polyubiquitin moieties from substrates such as RIP1. This negative feedback mechanism restrains pro‐inflammatory gene expression, while in other contexts OTUD7B is recruited to activated receptor complexes (for example, EGFR) to delay receptor degradation and sustain downstream signaling. Its ability to counteract APC/C‐mediated ubiquitination and influence cell cycle progression further underscores its role as a molecular “brake” on aberrant signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOTUD7B’s regulatory functions extend into the control of receptor signaling dynamics, stress responses, and tumorigenesis. By modulating the ubiquitination status of components in the mTORC2 complex, it influences AKT activation and cellular growth signals. OTUD7B also has been implicated in regulating hypoxia‐inducible factors (HIFs) by controlling the levels or stability of transcription factors such as HIF‐1α and HIF‐2α, thereby linking its deubiquitinating activity to cellular adaptation under low oxygen conditions and contributing to oncogenic processes. In breast and lung cancer cells, OTUD7B can stabilize hormone receptors and other signaling molecules to promote cell proliferation, migration, and survival under stress conditions including hyperthermia. Moreover, its role in the DNA damage response involves orchestrating ubiquitin “cross‐talk” at sites of damage, thus influencing the recruitment of repair complexes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Paul C Evans, Trevor S Smith, Meng-Jiun Lai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel type of deubiquitinating enzyme."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M301863200"}], "href": "https://doi.org/10.1074/jbc.M301863200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12682062"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12682062"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Anja Bremm, Stefan M V Freund, David Komander "}, {"type": "b", "children": [{"type": "t", "text": "Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Struct Mol Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nsmb.1873"}], "href": "https://doi.org/10.1038/nsmb.1873"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20622874"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20622874"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Tycho E T Mevissen, Yogesh Kulathu, Monique P C Mulder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Molecular basis of Lys11-polyubiquitin specificity in the deubiquitinase Cezanne."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature19836"}], "href": "https://doi.org/10.1038/nature19836"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27732584"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27732584"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Julia Mader, Jessica Huber, Florian Bonn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oxygen-dependent asparagine hydroxylation of the ubiquitin-associated (UBA) domain in Cezanne regulates ubiquitin binding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA119.010315"}], "href": "https://doi.org/10.1074/jbc.RA119.010315"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31937588"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31937588"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Karine Enesa, Mustafa Zakkar, Hera Chaudhury, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NF-kappaB suppression by the deubiquitinating enzyme Cezanne: a novel negative feedback loop in pro-inflammatory signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M708690200"}], "href": "https://doi.org/10.1074/jbc.M708690200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18178551"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18178551"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Karine Enesa, Kazuhiro Ito, Le A Luong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hydrogen peroxide prolongs nuclear localization of NF-kappaB in activated cells by suppressing negative regulatory mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M801312200"}], "href": "https://doi.org/10.1074/jbc.M801312200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18474597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18474597"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "F Pareja, D A Ferraro, C Rubin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deubiquitination of EGFR by Cezanne-1 contributes to cancer progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2011.587"}], "href": "https://doi.org/10.1038/onc.2011.587"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22179831"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22179831"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jia-hong Wang, Wei Wei, Zhi-xing Guo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased Cezanne expression is associated with the progression and poor prognosis in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Transl Med (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12967-015-0396-1"}], "href": "https://doi.org/10.1186/s12967-015-0396-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25638165"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25638165"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Thomas Bonacci, Aussie Suzuki, Gavin D Grant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cezanne/OTUD7B is a cell cycle-regulated deubiquitinase that antagonizes the degradation of APC/C substrates."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201798701"}], "href": "https://doi.org/10.15252/embj.201798701"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29973362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29973362"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Kunjan Harit, Rituparna Bhattacharjee, Kai Matuschewski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The deubiquitinating enzyme OTUD7b protects dendritic cells from TNF-induced apoptosis by stabilizing the E3 ligase TRAF2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-023-06014-5"}], "href": "https://doi.org/10.1038/s41419-023-06014-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37516734"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37516734"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Imelda Rosalyn Sianipar, Chieko Matsui, Nanae Minami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Physical and functional interaction between hepatitis C virus NS5A protein and ovarian tumor protein deubiquitinase 7B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Microbiol Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/1348-0421.12278"}], "href": "https://doi.org/10.1111/1348-0421.12278"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26112491"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26112491"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Sonia Moniz, Daniel Bandarra, John Biddlestone, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cezanne regulates E2F1-dependent HIF2α expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.168864"}], "href": "https://doi.org/10.1242/jcs.168864"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26148512"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26148512"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Zhaofei Pang, Lixuan Cui, Nan Ding, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expressions of insulin-like growth factor receptor-1 and cezanne-1 in lung adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Oncol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12032-017-0934-1"}], "href": "https://doi.org/10.1007/s12032-017-0934-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28365890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28365890"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Bin Wang, Zuliang Jie, Donghyun Joo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2 signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature22344"}], "href": "https://doi.org/10.1038/nature22344"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28489822"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28489822"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Jia-Hong Wang, Xiao-Ping Zhong, Yong-Fa Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cezanne predicts progression and adjuvant TACE response in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2017.428"}], "href": "https://doi.org/10.1038/cddis.2017.428"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28880268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28880268"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Jianing Tang, Zeyu Wu, Zelin Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OTUD7B stabilizes estrogen receptor α and promotes breast cancer cell proliferation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-021-03785-7"}], "href": "https://doi.org/10.1038/s41419-021-03785-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34035221"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34035221"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Xiao Wu, Shichang Liu, Cari Sagum, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crosstalk between Lys63- and Lys11-polyubiquitin signaling at DNA damage sites is driven by Cezanne."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.332395.119"}], "href": "https://doi.org/10.1101/gad.332395.119"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31699778"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31699778"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Weiwei An, Le A Luong, Neil P Bowden, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cezanne is a critical regulator of pathological arterial remodelling by targeting β-catenin signalling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cardiovasc Res (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/cvr/cvab056"}], "href": "https://doi.org/10.1093/cvr/cvab056"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33599243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33599243"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Zijun Guo, Lin Guo "}, {"type": "b", "children": [{"type": "t", "text": "OTUD7B deubiquitinates and stabilizes YAP1 to upregulate NUAK2 expression, thus accelerating gastric cancer procession."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dig Liver Dis (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.dld.2023.06.026"}], "href": "https://doi.org/10.1016/j.dld.2023.06.026"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37429790"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37429790"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Chao Sun, Jun Bai, Jingying Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "OTU deubiquitinase 7B facilitates the hyperthermia-induced inhibition of lung cancer progression through enhancing Smac-mediated mitochondrial dysfunction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Environ Toxicol (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/tox.24080"}], "href": "https://doi.org/10.1002/tox.24080"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38088504"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38088504"}]}]}]}