Ask about this productRelated genes to: UBE2J1 Blocking Peptide
- Gene:
- UBE2J1 NIH gene
- Name:
- ubiquitin conjugating enzyme E2 J1
- Previous symbol:
- -
- Synonyms:
- HSPC153, CGI-76, NCUBE1, UBC6
- Chromosome:
- 6q15
- Locus Type:
- gene with protein product
- Date approved:
- 2002-11-26
- Date modifiied:
- 2016-03-14
Related products to: UBE2J1 Blocking Peptide
Related articles to: UBE2J1 Blocking Peptide
- The SEL1L-HRD1 complex represents the most evolutionarily conserved branch of endoplasmic reticulum-associated degradation (ERAD), with SEL1L acting as a key cofactor for the E3 ubiquitin ligase HRD1. While the physiological relevance of this complex has been increasingly recognized, whether SEL1L is strictly required for HRD1 function in mammals has remained unclear. Here, using complementary in vivo and in vitro approaches, we define the architecture and physiological significance of the mammalian SEL1L-HRD1 ERAD complex. Our data demonstrate that direct binding between SEL1L and HRD1 is essential for ERAD function and neonatal survival in mice. In three knock-in mouse models harboring targeted mutations at the SEL1L-HRD1 interface, we show that the L709P variant - unlike the benign P699T mutation - results in complete neonatal lethality within 30 hours of birth, a phenotype more severe than that of the partially lethal S658P variant. Mechanistically, the L709P mutation abolishes SEL1L-HRD1 interaction, disrupting substrate engagement and impairing recruitment of the E2 enzyme UBE2J1, leading to the accumulation and aggregation of misfolded proteins in the ER. Notably, these defects can be partially rescued by HRD1 overexpression, echoing findings from yeast. Together, our results provide definitive evidence that the SEL1L-HRD1 interaction is essential for ERAD activity and neonatal viability in mammals, resolving a long-standing question in ERAD biology and identifying a new therapeutic strategy for modulating ERAD activity in humans. - Source: PubMed
Publication date: 2025/08/02
Zhang XiaweiLin Liangguang LeoPan LinxiuWei XiaoqiongWang Huilun HelenLi Zexin JasonQi Ling - Numerous studies have emphasized the importance of the ubiquitin-proteasome system (UPS) in the malignant progression of ovarian cancer (OC). However, whether ubiquitination-related genes (UbRGs) can be used to predict the prognosis of OC remains to be revealed. Patients with OC were divided into two clusters based on the expression of UbRGs, and prognosis was compared between the two clusters. A prognostic model was established based on UbRGs, and its predictive efficiency was validated using Kaplan-Meier (K-M) curves, receiver operating characteristic (ROC) curves, and a nomogram. Immune infiltration and gene mutation analyses were used to examine the effects of UbRGs on the prognosis of OC. The prognostic model served as a valid and independent predictor of OC prognosis. Immune infiltration revealed that the unique immune microenvironment of OC was regulated by UbRGs. Gene mutation analysis indicates that UbRGs likely influence OC malignant behavior by modulating gene mutation patterns. In addition, Ube2j1 was found to play an important role in regulating the malignant progression of OC. Furthermore, the mechanism by which Ube2j1 modulates the OC phenotype and reshapes its immune microenvironment via the JAK2/STAT3/PD-L1 pathway was elucidated, providing novel insights into the potential for ubiquitination-based immunotherapy in OC. This study provides novel insights into precision immunotherapy based on UbRGs in OC. The UbRGs-based prognostic model may help to provide novel insights for the application of ubiquitination-based immunotherapy in OC. - Source: PubMed
Publication date: 2025/07/15
Zhao ShuLin XiaojingHuang YuyingKang ZhongminLuo HualiZhang QizhuLi QinshanLi Mengxing - Ischemic stroke (IS) constitutes a severe neurological disorder with restricted treatment alternatives. Recent investigations have disclosed that glycosylation is closely associated with the occurrence and outcome of IS. Nevertheless, data on the transcriptomic dynamics of glycosylation in IS are lacking. The objective of this study was to undertake a comprehensive exploration of glycosylation-related genes (GRGs) in IS via bioinformatics and to assess their immune characteristics. In this study, through the intersection of genes from weighted gene co-expression network analysis, GRGs from five glycosylation pathways, and DEGs from differential expression analysis, 20 candidate GRGs were identified. Subsequently, through LASSO, Random Forest, and SVM-RFE, 3 hub GRGs (F5, PPP6C, and UBE2J1) were identified. Additional, a gene diagnostic model linked to glycosylation was developed and validated. The findings indicated that the diagnostic model could effectively distinguish between IS patients and healthy individuals in the training, validation, and merging datasets, indicating clinical relevance. Subsequently, by employing unsupervised clustering analysis, IS patients were classified into three clusters, and significant disparities were witnessed in immune cell infiltration among distinct clusters. In summary, this study successfully identified hub GRGs in IS and investigated the roles of these hub genes in the immune microenvironment, indicating potential clinical applications for IS. - Source: PubMed
Publication date: 2025/04/29
Zhang HuiJi YananYi ZhongquanZhao JingLiu JianpingZhang Xianxian - The RING-type E3 ubiquitin-protein ligase MuRF1 (also known as TRIM63) plays an important role in skeletal muscle atrophy by targeting contractile proteins. In cellulo, MuRF1 can alternatively interact with four E2 enzymes (UBE2E1, UBE2J1, UBE2J2, or UBE2L3), suggesting different functions or targets for the four MuRF1-E2 complexes. In this article, we studied the interface of these MuRF1-UBE2 complexes based on AlphaFold2 and AlphaFold3 predictions. These predictions revealed the involvement of different residues at the interface of each complex. We confirmed this overall interface difference by the differential sensitivity of MuRF1-E2 complexes to regenerating solutions in surface plasmon resonance experiments. We further confirmed several predictions individually by affinity measurements with point-mutant E2 enzymes and truncated MuRF1. We used the interaction-induced fluorescence change approach with fluorescent MuRF1. Besides canonical E2-RING-type E3 interactions, we were able to identify selective contact points between MuRF1 and its UBE2 partners. Furthermore, in the case of the MuRF1-E2E1 pair, unlike the other MuRF1-E2 pairs, the interaction may also be governed by a domain outside the RING domain. Since the function of RING-type E3s is regulated by E2 enzymes, deciphering the mechanisms of selective recruitment of E2s by MuRF1 paves the way for the development of targeted therapeutics to fight muscle atrophy. - Source: PubMed
Publication date: 2025/02/10
Claustre AgnèsMalige MélodieMacheton MaëlysCombaret LydieLefai EtienneFafournoux PierreTaillandier DanielHenri JulienPolge Cécile - Immune cells within tumor tissues play important roles in remodeling the tumor microenvironment, thus affecting tumor progression and the therapeutic response. The current study was designed to identify key markers of plasma cells and explore their role in high-grade serous ovarian cancer (HGSOC). - Source: PubMed
Publication date: 2025/01/28
Tian YunjieDong RuoyuGuan YingxiaWang YingZhao WeiZhang JunKang Shan