Ask about this productRelated genes to: PELI1 antibody
- Gene:
- PELI1 NIH gene
- Name:
- pellino E3 ubiquitin protein ligase 1
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 2p14
- Locus Type:
- gene with protein product
- Date approved:
- 2000-09-01
- Date modifiied:
- 2016-10-05
Related products to: PELI1 antibody
Related articles to: PELI1 antibody
- Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), represent a major and growing public health burden. Neuroinflammation is a critical driver of pathology in these disorders, and the ubiquitin-proteasome system (UPS) has emerged as a central regulator of inflammatory signaling within the nervous system. This review systematically examines the molecular interplay between the UPS and neuroinflammation in the progression of AD and PD. - Source: PubMed
Publication date: 2026/04/11
Guo YouweiWang NingyanTao ZheHuang XiangfeiYu WenZeng JiaxueLiu XiongtaoChen ShibiaoHua FuzhouWang Xifeng - Inflammatory activation is a central mechanism driving the progression of Diabetic Kidney Disease (DKD). Pyroptosis, a type of programmed cell death linked to inflammation, contributes significantly to this process. The involvement of the NLRP3 inflammasome-triggered pyroptosis pathway in DKD pathogenesis, however, requires further clarification. Pellino1, an E3 ubiquitin ligase that modulates NLRP3 inflammasome function, has been associated with multiple acute and chronic inflammatory conditions, yet its specific function in DKD is not well established. Our study revealed that Pellino1 expression is elevated in renal tissues from DKD patients and db/db mice. This increase correlated with activation of NLRP3 inflammasome-mediated pyroptosis, infiltration of macrophages into the renal interstitium, and the development of fibrosis. In vitro, high glucose (HG) stimulation enhanced the expression of both Pellino1 and key proteins involved in pyroptosis within renal tubular epithelial cells. Mechanistically, Pellino1 overexpression augmented NLRP3 inflammasome-dependent pyroptosis, an effect potentially attributable to its promotion of K63-linked ubiquitination of ASC. In contrast, either silencing Pellino1 or administering a Pellino1 inhibitor suppressed the activation of the NF-κB pathway and NLRP3-driven pyroptosis in diabetic kidneys and in HG-stimulated tubular cells. Together, these results position Pellino1 as a potential therapeutic target for alleviating inflammatory injury and fibrotic damage in DKD. - Source: PubMed
Zhou XingyanZhang RuiGuo ZiweiYang YuxingYan Rui - Ubiquitination serves a critical role in regulating both inflammatory responses and kidney injury. Among inherited renal disorders, autosomal dominant polycystic kidney disease (ADPKD) has demonstrated associations with disrupted ubiquitin signaling that exacerbates inflammation and cyst progression. In this study, we demonstrate that the E3 ligase Pellino1 (Peli1) acts as an essential contributor to the pathogenesis of ADPKD amid inflammatory conditions. In individuals with clear cell renal cell carcinoma (ccRCC), Peli1 exhibits markedly elevated expression, and this upregulation is associated with adverse clinical outcomes. Additionally, we find that various TLR stimulations in renal tubular cells induce increased Peli1 expression, which is also elevated in samples from ADPKD patients. Using doxycycline-inducible Peli1-transgenic mice, we establish that Peli1 overexpression leads to impaired renal function and facilitates cyst formation. On a mechanistic level, elevated Peli1 promotes cystic epithelial cell proliferation by activating mTOR signaling, accomplished through the stabilization of S6K1. In summary, our data indicate that TLR-driven upregulation of Peli1 facilitates renal cyst growth via S6K1 stabilization. These results reveal a novel mechanistic link between PKD and ccRCC. A schematic model is proposed to describe the role of Peli1 in the development of polycystic kidney diseases. Normal signaling pathways (Left) and Peli1-mediated signaling pathways in polycystic kidney disease (Right). The illustration outlines the cascade from TLR stimulation to Peli1-dependent K63 ubiquitination of S6K1 and subsequent proliferation in renal tubular epithelial cells. This figure was generated using BioRender.com. - Source: PubMed
Publication date: 2026/03/05
Kim SuhyeonKim Min-HeeKo Bo-KyoungKim Kyung-MoWang NaiyuJo Su-MiGo HeounjeongPark Eun-JiLee Chang-Woo - The enrichment of CD4+ regulatory T cells (Tregs) drives gastric cancer immunosuppression. Revealing the underlying mechanisms driving Treg differentiation could help develop strategies to stimulate anti-tumor immunity. Serglycin, derived from tumor cells, facilitates tumor progression in gastric cancer primarily via its receptor CD44, which is highly expressed in T cells, especially Tregs. This study investigated the immunomodulatory functions of tumor cell-derived serglycin in gastric cancer. Analysis of an integrated single-cell RNA-sequencing dataset of 23 paired gastric cancer tissues and adjacent normal gastric mucosa tissues revealed that Tregs were enriched in the gastric cancer tissues and associated with serglycin levels. Functionally, serglycin promoted differentiation of a specific subset of LAG3+ Tregs and maintained their suppressive function by activating the CD44/TGFβRI/Smad3 signaling pathway. Mechanistically, serglycin-CD44 signaling triggered glycolysis and facilitated ROS clearance, which attenuated the M171 oxidative modification of LAG3. Reduced oxidation led to enhanced LAG3 dimerization while disrupting the interaction with PELI1 to suppress K48-linked ubiquitination and degradation of LAG3, leading to LAG3 upregulation in Tregs. Blocking serglycin-CD44 signaling suppressed LAG3+ Treg differentiation and function, relieved immunosuppression, and inhibited tumor progression. Collectively, these findings identify a serglycin-CD44-mediated glycolysis-oxidation-ubiquitination cascade that functions as a critical driver of LAG3+ Treg differentiation in gastric cancer and provide pre-clinical evidence for targeting this axis to improve immunotherapeutic efficacy. - Source: PubMed
Publication date: 2026/02/24
Wang QingyuanXu PengChen JiaYang ShengLi XiangWang YaohuiHua HongjinPing XiaochunShen JiajiaShen Lizong - To evaluate the impact of bone metastasis on the prognosis of lung adenocarcinoma patients receiving first-line third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and to explore the potential mechanisms by which bone metastasis contributes to EGFR-TKI resistance. A retrospective analysis was conducted on the clinical data of 370 EGFR-mutant advanced lung adenocarcinoma patients who received first-line treatment with third-generation EGFR-TKI at the First Affiliated Hospital of Nanjing Medical University from January 2019 to June 2024, with follow-up until June 2024. Progression-free survival (PFS) and overall survival (OS) were compared between patients with and without baseline bone metastasis. Survival curves were generated using the Kaplan-Meier method, and differences between groups were assessed by the log-rank test. Univariate and multivariate Cox proportional hazards regression models were applied to identify factors associated with PFS following third-generation EGFR-TKI treatment. Single-cell RNA sequencing (scRNA-seq) was performed on two primary pulmonary tumors and two bone metastatic lesions to characterize transcriptomic differences in cancer cells and immune cells within the tumor microenvironment. Gene Ontology (GO) enrichment analysis was applied to identify bone metastasis-specific signaling pathways. Based on immune regulatory genes upregulated in cancer cells from bone metastatic lesions, an immune-regulatory score was constructed using a LASSO-Cox regression model in a training cohort of EGFR-mutant lung adenocarcinoma patients from The Cancer Genome Atlas (TCGA). Patients in both the training cohort and an independent Asian EGFR-mutant lung adenocarcinoma validation cohort were stratified into high-and low-score groups according to the median immune regulatory score, and OS was compared between groups. Among the 370 lung adenocarcinoma patients receiving first-line third-generation EGFR-TKI treatment, 161 patients had baseline bone metastasis (mean age 60±11 years; 70 males), while 209 patients had no baseline bone metastasis (mean age 61±9 years; 80 males). No significant differences in baseline clinicopathological characteristics were observed between patients with and without bone metastasis (all >0.05). The median PFS in the bone metastasis group was 27.5 months (95%: 22.0-33.1), which was significantly shorter than that in the non-bone metastasis group [59.0 months (95%: 32.8-85.1), <0.001]. The median OS was 46.2 months (95%: 40.4-51.9) in the bone metastasis group, whereas the median OS had not yet been reached in the non-bone metastasis group, with a statistically significant difference (=0.013). Multivariate Cox regression analysis identified bone metastasis as an independent risk factor for PFS (=1.74, 95%:1.27-2.37, <0.001). Cancer cells in bone metastatic lesions exhibited upregulation of C-X-C motif chemokine ligand 17 (CXCL17), complement decay-accelerating factor (CD55), interferon regulatory factor 1 (IRF1), E3 ubiquitin-protein ligase pellino homolog 1 (PELI1), solute carrier family 7 member 5 (SLC7A5) and prostaglandin-endoperoxide synthase 2 (PTGS2), which were predominantly enriched in pathways related to immune cell differentiation, chemotaxis, and inflammatory responses. At the immune cell level, lymphoid cells in bone metastatic lesions showed activation of stress response and apoptotic pathways, whereas myeloid cells demonstrated significant activation of cytokine/chemokine signaling and inflammation-related pathways. An immune-regulatory score based on CXCL17, CD55, IRF1, PELI1, SLC7A5, and PTGS2 was constructed. In the TCGA training cohort, the median OS of 41 patients with a high immune-regulatory score was 23.1 months (95%: 17.5-28.7), which was significantly shorter than that of patients with a low score [58.5 months (95%: 43.0-73.9), <0.001]. In the independent Asian cohort of 93 EGFR-mutant lung adenocarcinoma patients, the median OS of 46 patients with a high immune-regulatory score was 85.3 months (95%: 80.0-not reached), while the median OS in the low-score group was not reached, with a statistically significant difference (=0.014). Bone metastasis is an adverse prognostic factor for progression-free survival in lung adenocarcinoma patients treated with third-generation EGFR-TKIs. Bone metastasis lesions exhibit a distinct immunosuppressive tumor microenvironment in EGFR-mutant advanced lung adenocarcinoma, in which upregulation of immune regulatory genes in cancer cells and dysfunction of immune cells may constitute a potential mechanism underlying resistance to third-generation EGFR-TKIs. - Source: PubMed
Publication date: 2026/02/12
Zhang CShi X LJiang Y QLi JXu J LGuo R H