Ask about this productRelated genes to: UBE2L3 Blocking Peptide
- Gene:
- UBE2L3 NIH gene
- Name:
- ubiquitin conjugating enzyme E2 L3
- Previous symbol:
- -
- Synonyms:
- UBCH7
- Chromosome:
- 22q11.21
- Locus Type:
- gene with protein product
- Date approved:
- 1997-03-21
- Date modifiied:
- 2016-10-05
Related products to: UBE2L3 Blocking Peptide
Related articles to: UBE2L3 Blocking Peptide
- Genome-wide association studies (GWASs) have identified at least 17 genetic variants associated with gastric cancer risk. However, the underlying genetic regulatory mechanisms remain poorly understood. We systematically performed genome-wide analyses of expression quantitative trait loci (eQTLs), splicing QTLs (sQTLs), and alternative polyadenylation QTLs (apaQTLs) using gastric biopsy tissues from 262 Chinese individuals, and we integrated these data with GWAS results from 10,254 gastric cancer cases and 10,914 controls. We identified 4,636 eGenes, 1,422 sGenes, and 511 apaGenes, with 55.3% of sGenes and 49.5% of apaGenes being distinct from eGenes. Notably, over half of the variants associated with shared genes were unique to a specific QTL type, with these variants characterized by a wide physical separation (median distance = 25.01 kb) and weak linkage disequilibrium (median r = 0.42). Gastric cancer risk variants showed significant enrichment across all three QTL categories. Integrative transcriptome-wide association studies (TWASs) across expression, splicing, and alternative polyadenylation identified 34 genes at false discovery rate (FDR) <0.05; PSCA was implicated across all three regulatory layers. The candidates DIP2B and RMC1 were experimentally validated to promote gastric tumorigenesis both in vitro and in vivo. Functional analyses revealed that the rs11264361-T allele reduced FDPS exon 9 skipping, leading to increased expression of the full-length transcript, while the apaVariant rs7445 regulated UBE2L3 polyadenylation via ATXN2 binding, contributing to gastric cancer risk. Collectively, these results provide a comprehensive QTL resource in gastric tissues and demonstrate distinct regulatory mechanisms of eQTLs, sQTLs, and apaQTLs in gastric cancer development. - Source: PubMed
Hu BeipingZhang MinYu YuhuiLiu YongchaoWang JiaweiZhang AipingLi QianGao YunLi ZheBian LijunGu YuanliangZhu XiaShe QiangGao XuefengDeng BinFang HaishengHu CaihongChen YuhengChen YanWang XinyaYin XianyongZhu MengWang LuJiang YueChen JiapingDai JunchengMa HongxiaDing YanbingYan CaiwangJin Guangfu - Triple-negative breast cancer (TNBC), a distinct breast cancer subtype, poses significant challenges to conventional therapeutic approaches, and effective targeted therapies are limited. CRISPR/Cas9 library screening has demonstrated unprecedented efficiency and revolutionary potential in the identification of therapeutic targets. In this study, we performed CRISPR/Cas9 library screening and identified the E2 ubiquitin-conjugating enzyme UBE2L3 as a critical regulatory factor in the progression of TNBC. Loss of UBE2L3 restricted tumor cell growth by modulating autophagy in TNBC cells. Mechanistically, UBE2L3 downregulation led to increased tuberous sclerosis complex 2 (TSC2) expression, suppressing mTOR activity and altering autophagic processes in tumor cells. This regulation was mediated through the interaction between UBE2L3 and the E3 ubiquitin ligase SMURF2, which together control TSC2 protein ubiquitination and degradation. Autophagy and the tumor microenvironment are closely associated, and we observed that UBE2L3 knockdown in TNBC tumors significantly increased CD8+ T lymphocyte infiltration and enhanced tumor sensitivity to anti-PD-1 therapy. Collectively, our findings provide a theoretical foundation for considering UBE2L3 as a potential therapeutic target in TNBC. - Source: PubMed
Publication date: 2026/02/18
Xu JianCheng LingMa SienGan ChenChai JiayingZheng XinyiHu LongyuLing MeiwenZhang MingjunZhao BaoCheng Huaidong - Non-Coding regions contains genomic remnants called as Pseudogenes. For a long time, pseudogenes have been regarded as non-functional. This study investigates the previously unstudied Pseudogene CDC27P9 role in cervical cancer. Whole RNA-transcriptome profiling was performed from blood samples of n = 10 cervical cancer patients and n = 10 age matched healthy controls. CDC27P9 expression was validated in patient samples using RT-PCR. The putative CDC27P9-encoded protein structure was predicted using ChimeraX 1.9, refined predicted protein using (GROMACS 2022.2) and evaluated by Ramachandran plot. Post docking using (HADDOCK2.4) with parent gene CDC27 and other interacting genes, a 100ns MD Simulation (GROMACS 2022.2) was done. Functional studies done by siRNA-mediated silencing of CDC27P9 in HeLa cells to study Anaphase Promoting Complex/Cyclosome Pathway using RT-PCR. Cell Cycle, Mitochondrial Membrane Potential Loss and Apoptosis, using Flow Cytometry. Cell death and Chromatin Condensation was visualised using Laser Scanning Confocal Microscopy and validated in multimode microplate reader. Transcriptome sequencing revealed CDC27P9 upregulated with logFC = 10.68. RT-PCR validated overexpression of CDC27P9 in cervical cancer patients. Putative CDC27P9-encoded protein had an 93.11% of the residues point to protein structure reliability. Molecular docking and MD simulation showed strongest interactions with CDC27 and CDC20. Silencing of CDC27P9, downregulated CDC27 and Anaphase Promoting Complex/Cyclosome genes UBE2L3, PTTG1, ESPL1. In parallel downregulation of anti-apoptotic gene BCL2 while upregulation of pro-apoptotic BAX was observed. Silencing of CDC27P9 induced cell cycle arrest at S-phase, induces apoptosis and mitochondrial membrane potential loss. Observation of Condensed chromatin structure post silencing was an indicative of apoptotic signalling. Further cell death, growth inhibition and morphology changes was observed. Interestingly, silencing of CDC27P9 in cervical cancer HeLa cells caused downregulation of HPV 18. This study is the first to identify pseudogene CDC27P9 as functional with active transcripts and putative protein‑coding potential. Our findings suggest that CDC27P9 may contribute to cervical cancer progression by modulating APC/C‑mediated cell‑cycle pathways, prevent apoptosis thereby sustains cell survival in cancer cells and could be involved in HPV18-associated cellular pathways. - Source: PubMed
Publication date: 2026/03/24
Antony Edwin Rodrigues FenwickKrishnan DeenaAbbas Hussein HameedRaj Minu Jenifer MichaelSubramani SasikalaLakshman NathishJustin AntonyGovindaraj SangamiRamasamy Sivasamy - Glaucoma trabecular meshwork (GTM) cells cultured in vitro retain many characteristics of their in situ phenotype. Here, we used isobaric tandem mass tags (TMTpro) to label peptides from glaucomatous and non-glaucomatous TM (NTM) cells to identify differentially regulated proteins. Confluent NTM (n = 5) and GTM (n = 5) cells were lysed, proteins were trypsin digested, and peptides were labeled with 18-plex TMTpro. TMT-labeled peptides were fractionated on an Orbitrap Fusion mass spectrometer and data were processed using the PAW/Comet pipeline and EdgeR with Benjami–Hochberg multiple correction testing. Isobaric multiplexed quantitative proteomics identified 206 proteins that were significantly (FDR < 0.1) upregulated in GTM cells, 42 proteins that were downregulated, with 5270 non-candidates. Significant regulated pathways included extracellular matrix (DCN, COL4A1, CHI3L1), Wnt signaling (FZD1, FZD7, GSK3B), cytoskeletal regulation (ROCK2, MSN, TPM2, VIM, NF2), protein degradation (USP9X, LAMP1, SYNV1, UBE2L3), and nuclear proteins (LMNA, DFFA, CHMP3, RAD21). Western immunoblotting studies confirmed the TMTpro data. Immunofluorescence showed that the SNX7-stained nucleoli of GTM cells were significantly (p < 0.05) larger, and the DIAPH2 immunostaining was more distended into the cytosol than in NTM cells. This study identified many significantly regulated proteins in cultured GTM cells, and the results revealed several new avenues for developing clinical therapies for glaucoma patients. - Source: PubMed
Publication date: 2026/03/18
Holden PaulSun Ying YingZientek KeithWilmarth Phillip AReddy Ashok PKeller Kate E - E3 ligases partner with E2 enzymes to regulate vast eukaryotic biology. The hierarchical nature of these pairings, with >600 E3s and ~40 E2s in humans, necessitates that E2s cofunction with numerous different E3s. Here, focusing on E3s in the RING-between-RING (RBR) family and their partner UBE2L3 and UBE2D-family E2s, we report an approach to interrogate selected pathways. We screened phage-displayed libraries of structure-based E2 variants (E2Vs) to discover enzymes with enhanced affinity and specificity toward half of all RBR E3 ligases (ARIH1, ARIH2, ANKIB1, CUL9, HOIL1, HOIP, and RNF14). Collectively, these E2Vs allowed distinguishing actions of different cofunctioning E3s, obtaining high-resolution cryogenic Electron Microscopy (cryo-EM) structures of an RBR E3 in the context of a substrate-bound multiprotein complex, and profiling an endogenous RBR E3 response to an extracellular stimulus. Overall, we anticipate that E2V technology will be a generalizable tool to enable in-depth mechanistic and structural analysis of E3 ligase functions, and mapping their activity states and protein partners in cellular signaling cascades. - Source: PubMed
Publication date: 2026/01/02
Du JialeAndree Gisele AHorn-Ghetko DanielStier LucaSingh JaspalKostrhon SebastianKiss LeoMann MatthiasSidhu Sachdev SSchulman Brenda A