{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNote: Although the query mentions LARGE‐AS1, the provided abstracts focus on UBE2T. UBE2T, a ubiquitin‐conjugating enzyme, is frequently overexpressed in malignancies and plays a pivotal role in promoting the cancerous phenotype. In lung cancer, for example, UBE2T is markedly upregulated compared with normal lung tissue. Its expression correlates with enhanced tumorigenic properties such as increased colony formation in soft agar, indicating that UBE2T contributes to the malignant cell phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn glioblastoma, UBE2T overexpression similarly underpins tumor progression. It promotes proliferation, invasion, and resistance to apoptosis. Mechanistically, UBE2T acts by directly ubiquitinating ribosomal protein L6 (RPL6), triggering its degradation via K48‐linked polyubiquitination—a process that occurs independently of a traditional E3 ligase. This degradation not only diminishes the expression of wild‐type p53 but can also augment the gain‐of‐function effects of mutant p53, thereby exacerbating the malignant behavior of GBM cells. In addition, emerging evidence explores its role in mediating temozolomide resistance in glioblastoma."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its oncogenic functions, UBE2T is crucial for genomic stability during development. In the context of primordial germ cells (PGCs), UBE2T is an essential component of the Fanconi anemia (FA) pathway. Its activity in ubiquitylating the FANCD2-FANCI complex not only activates the FA pathway but also helps resolve transcription-replication conflicts by targeting R-loops. This dual function stabilizes replication forks and protects common fragile sites, thereby ensuring proper PGC proliferation and minimizing DNA damage that leads to p53 activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jia Hao, Anjian Xu, Xiaolei Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Elevated expression of UBE2T in lung cancer tumors and cell lines."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Tumour Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1159/000148187"}], "href": "https://doi.org/10.1159/000148187"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18667844"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18667844"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xuxiu Tao, Xia Wu, Peijun Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UBE2T promotes glioblastoma malignancy through ubiquitination-mediated degradation of RPL6."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/cas.15604"}], "href": "https://doi.org/10.1111/cas.15604"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36156329"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36156329"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yang Wang, Ge Gao, Xiangpin Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UBE2T Promotes Temozolomide Resistance of Glioblastoma Through Regulating the Wnt/β-Catenin Signaling Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Drug Des Devel Ther (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/DDDT.S405450"}], "href": "https://doi.org/10.2147/DDDT.S405450"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37181827"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37181827"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yongze Yu, Weiwei Xu, Canxin Wen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "UBE2T resolves transcription-replication conflicts and protects common fragile sites in primordial germ cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-023-04733-8"}], "href": "https://doi.org/10.1007/s00018-023-04733-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36928776"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36928776"}]}]}]}