{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nHOPS/Tmub1 is a ubiquitously expressed, transmembrane ubiquitin‐like shuttling protein that plays a central role in the regulation of cell division and genomic stability. It localizes to centrosomes and associates with key cytosolic complexes to ensure proper centrosome duplication, mitotic spindle organization, and cytokinesis. Loss or depletion of HOPS/Tmub1 leads to supernumerary centrosomes, multinucleated cells, and cell cycle arrest, while distinct isoforms of the protein participate in assembling critical complexes with nucleophosmin (NPM) and the tumor suppressor p19Arf to enforce cell cycle checkpoints and inhibit tumor cell proliferation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its roles in mitosis, HOPS/Tmub1 is a potent regulator of apoptotic signaling in response to genotoxic stress. By binding to p53, it protects the tumor suppressor from proteasomal degradation and promotes its recruitment to the mitochondria, thereby amplifying the intrinsic apoptosis pathway. Reduced HOPS/Tmub1 levels, as seen in heterozygous or knockout models, result in impaired activation of p53‐dependent apoptosis and an attenuated DNA damage response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nHOPS/Tmub1 also contributes to the regulation of membrane trafficking and neuronal function. In the brain, it facilitates the recycling of the AMPA receptor subunit GluR2 back to the cell surface—thereby maintaining proper basal synaptic transmission—and interacts with the calcium modulating cyclophilin ligand (CAMLG) to influence locomotor activity and wakefulness. These functions highlight the protein’s importance in ensuring appropriate receptor localization and neuronal signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cell cycle regulation and neuronal activity, HOPS/Tmub1 is implicated in modulating inflammatory responses, organ regeneration, and cellular differentiation. It enhances NF‐κB activation by interacting directly with the E3 ubiquitin ligase TRAF6, leading to reduced IκBα stability and increased transcription of inflammatory mediators. In liver regeneration, HOPS/Tmub1 inhibits hepatocyte proliferation through suppression of STAT3 phosphorylation, establishing a negative feedback loop in STAT3 signaling. Moreover, in the eye lens the dynamic nucleocytoplasmic shuttling and association of HOPS/Tmub1 with crystallin proteins suggest a structural role in fiber differentiation and the maintenance of lens transparency."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Stefania Pieroni, Maria Agnese Della Fazia, Marilena Castelli, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HOPS is an essential constituent of centrosome assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.7.10.5882"}], "href": "https://doi.org/10.4161/cc.7.10.5882"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18418082"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18418082"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "M Castelli, S Pieroni, C Brunacci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatocyte odd protein shuttling (HOPS) is a bridging protein in the nucleophosmin-p19 Arf network."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/onc.2012.353"}], "href": "https://doi.org/10.1038/onc.2012.353"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22890319"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22890319"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Marilena Castelli, Danilo Piobbico, Daniela Bartoli, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Transmembrane and ubiquitin-like domain containing 1 (Tmub1) regulates locomotor activity and wakefulness in mice and interacts with CAMLG."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0011261"}], "href": "https://doi.org/10.1371/journal.pone.0011261"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20582322"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20582322"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hangwei Fu, Rui Dong, Yida Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tmub1 negatively regulates liver regeneration via inhibiting STAT3 phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2018.12.013"}], "href": "https://doi.org/10.1016/j.cellsig.2018.12.013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30610893"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30610893"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Marina Maria Bellet, Stefania Pieroni, Marilena Castelli, et al. 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