{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUBQLN1 is a multifunctional ubiquitin‐like adaptor protein defined by an N‐terminal ubiquitin‐like (UBL) domain and a C‐terminal ubiquitin‐associated (UBA) domain that plays a critical role in protein quality control. It facilitates the recognition and delivery of polyubiquitinated substrates to the proteasome and acts as a chaperone that prevents the aggregation of hydrophobic or misfolded proteins. In addition, UBQLN1 promotes autophagy by associating with autophagosomes and regulating their maturation and trafficking to lysosomes, contributes to endoplasmic reticulum–associated degradation (ERAD), and helps clear aberrant mitochondrial membrane protein precursors, thereby modulating the unfolded protein response."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn neural systems, UBQLN1 critically affects the metabolism of key proteins involved in neurodegenerative processes. It regulates amyloid precursor protein (APP) trafficking and its processing—which in turn influences amyloid‐β peptide generation—and modulates presenilin stability and γ‐secretase activity. By binding to aggregation‐prone molecules such as TDP‐43 and polyglutamine‐expanded proteins, UBQLN1 suppresses cytotoxic aggregate formation. Moreover, genetic and expression studies have investigated UBQLN1 variations in Alzheimer’s disease and related conditions, further underscoring its impact on neuronal proteostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOutside the nervous system, UBQLN1 exerts important regulatory functions on cell signaling and receptor trafficking that bear on cancer biology. It modulates the surface expression and turnover of receptors such as neuronal nicotinic acetylcholine and GABA(A) receptors and can influence the activity of growth factor receptors like IGF1R. These actions are linked to changes in cell migration, invasion, and epithelial-to-mesenchymal transition, thereby impacting radioresistance and drug resistance in various cancers. In several studies, altered UBQLN1 expression has been correlated with aggressive clinical features and poor patient outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "31", "end_ref": "41"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition, UBQLN1 has been implicated in the cellular response to viral infection. It interacts with viral RNA-dependent polymerases, such as that of hepatitis C virus, thereby promoting their ubiquitination and degradation. Through such mechanisms, UBQLN1 may help control viral replication and also participate in the broader regulation of innate immune signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "42", "end_ref": "44"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Diana L Ford, Mervyn J Monteiro "}, {"type": "b", "children": [{"type": "t", "text": "Dimerization of ubiquilin is dependent upon the central region of the protein: evidence that the monomer, but not the dimer, is involved in binding presenilins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20060441"}], "href": "https://doi.org/10.1042/BJ20060441"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16813565"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16813565"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Diana L Ford, Mervyn J Monteiro "}, {"type": "b", "children": [{"type": "t", "text": "Studies of the role of ubiquitination in the interaction of ubiquilin with the loop and carboxyl terminal regions of presenilin-2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi700604q"}], "href": "https://doi.org/10.1021/bi700604q"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17614368"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17614368"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Daoning Zhang, Shahri Raasi, David Fushman "}, {"type": "b", "children": [{"type": "t", "text": "Affinity makes the difference: nonselective interaction of the UBA domain of Ubiquilin-1 with monomeric ubiquitin and polyubiquitin chains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2007.12.029"}], "href": "https://doi.org/10.1016/j.jmb.2007.12.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18241885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18241885"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Alice Lu, Mikko Hiltunen, Donna M Romano, et al. 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