{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nUFC1 plays a critical dual role in cellular function. On one hand, it serves as an E2-like enzyme in the ufmylation cascade—a pathway analogous to ubiquitylation—where the ubiquitin‐fold modifier Ufm1 is first processed and activated by the E1‐like enzyme Uba5 and then transferred to UFC1 via a thioester bond formed at a key, solvent‐accessible active‐site cysteine. Structural and biochemical analyses have delineated a conserved catalytic core within UFC1, including a flexible loop harboring Cys116, and have revealed the unique interaction interfaces—such as with the C-terminal region of UBA5 and with potential substrates like NCAM—that underlie its specificity and efficiency in conjugating Ufm1 to target proteins."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOn the other hand, the term UFC1 is also used to denote a long noncoding RNA that has emerged as an important regulator in diverse pathophysiological contexts. Dysregulation of lncRNA UFC1 is implicated in cancer progression—for instance, by promoting hepatocellular carcinoma and non‐small cell lung cancer through mechanisms that include sequestering miR-34a and facilitating EZH2-mediated epigenetic silencing of tumor suppressors like PTEN. In contrast, reduced expression of lncRNA UFC1 in osteoarthritis correlates with impaired chondrocyte proliferation and enhanced apoptosis, suggesting a role in maintaining cartilage integrity. These findings underscore the multifaceted functions attributed to UFC1, whether as a component of the ufmylation machinery or as a regulatory RNA influencing cell survival and tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Masaaki Komatsu, Tomoki Chiba, Kanako Tatsumi, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "A Concerted Action of UBA5 C-Terminal Unstructured Regions Is Important for Transfer of Activated UFM1 to UFC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms22147390"}], "href": "https://doi.org/10.3390/ijms22147390"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34299007"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34299007"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Manoj Kumar, Prasanth Padala, Jamal Fahoum, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural basis for UFM1 transfer from UBA5 to UFC1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-25994-6"}], "href": "https://doi.org/10.1038/s41467-021-25994-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34588452"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34588452"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Chuanhui Cao, Jingyuan Sun, Dongyan Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The long intergenic noncoding RNA UFC1, a target of MicroRNA 34a, interacts with the mRNA stabilizing protein HuR to increase levels of β-catenin in HCC cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Gastroenterology (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1053/j.gastro.2014.10.012"}], "href": "https://doi.org/10.1053/j.gastro.2014.10.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25449213"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25449213"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Gang Zhang, Yadi Wu, Dong Xu, et al. 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