Ask about this productRelated genes to: MGRN1 Blocking Peptide
- Gene:
- MGRN1 NIH gene
- Name:
- mahogunin ring finger 1
- Previous symbol:
- -
- Synonyms:
- KIAA0544, RNF156
- Chromosome:
- 16p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-01-15
- Date modifiied:
- 2016-10-24
Related products to: MGRN1 Blocking Peptide
Related articles to: MGRN1 Blocking Peptide
- Acute lung injury (ALI) is a common respiratory disease worldwide, and obesity is a significant factor contributing to its progression. However, there is still a lack of effective clinical interventions specifically targeting this condition. This study aims to investigate the role of MGRN1 in obesity-related ALI. An obesity-related ALI mouse model was induced by a high-fat diet (HFD) and intratracheal instillation of lipopolysaccharide (LPS). An in vitro model was constructed using palmitic acid (PA) and LPS to stimulate mouse lung epithelial cells (MLE-12). Lung wet/dry weight ratio and HE staining were used to assess pathological changes in lung tissue. Cell damage was evaluated through CCK-8 and LDH release assays. Mitochondrial function was assessed via JC-1, Mito-Tracker Green, MitoSOX Red staining, and ATP content measurement. Additionally, RT-qPCR, Western blot, ELISA, immunofluorescence, and immunohistochemistry were employed to detect the expression of related genes and proteins.MGRN1 is downregulated in obesity-related ALI, and its overexpression alleviates LPS-induced lung histopathological damage in obese mice, reduces TNF-α, IL-1β, IL-6, ROS, and LDH levels, and inhibits PA-LPS-induced MLE-12 cell injury. Additionally, overexpression of MGRN1 restores mitochondrial function in PA-LPS-induced MLE-12 cells and suppresses PINK1/Parkin signaling pathway-mediated mitophagy. Further studies found that treatment with the PINK1 activator MTK458 attenuates the protective effect of MGRN1 overexpression on MLE-12 cells exposed to PA-LPS. MGRN1 restores mitochondrial function by inhibiting PINK1/Parkin-mediated mitophagy, thereby suppressing lung epithelial cell injury and ultimately alleviating obesity-related ALI. These findings suggest that MGRN1 may be a promising therapeutic target and that strategies aimed at restoring MGRN1 or pharmacologically restraining PINK1/Parkin-mediated mitophagy may offer a novel intervention for obese patients at risk of ALI, providing a theoretical basis for future clinical drug development. - Source: PubMed
Publication date: 2026/07/28
Wang YingpingLu LimingJin HuiWu JieLi XinChen ZhijuanLuo Lisi - Dysregulation of the ubiquitin-proteasome system (UPS) promotes tumorigenesis, but population-level evidence linking UPS variants to lung cancer risk is limited. - Source: PubMed
Publication date: 2026/05/29
Mao JianingLeng LingyunZhu TianyiWang JiayiZhao GenmingLiu XingLiu HongliangWu YilingCheng LeiZhang Ruoxin - Receptor-type E3 ubiquitin ligases enable extracellular signals to control ubiquitylation in the cytoplasm, playing widespread roles in development, metabolism, and immunity. Using cryoelectron microscopy, integrated with biophysical and functional studies, we visualized a human E3 complex composed of two transmembrane proteins, MEGF8 and MOSMO, and the intracellular RING-family protein MGRN1. This MEGF8-MOSMO-MGRN1 (MMM) complex attenuates Hedgehog signaling by ubiquitylating Smoothened (SMO), a G-protein-coupled receptor (GPCR) that transduces morphogen signals. A long helix in the MMM complex engages SMO using an intramembrane degron and extends into the cytoplasm to suspend an activated and precisely oriented RING domain below the plasma membrane. This architecture enables ubiquitylation of the cytoplasmic surface of SMO, reducing SMO abundance at primary cilia. Our structure provides insights into MEGF8 mutations, which cause multi-organ birth defects, and defines a paradigm for how transmembrane E3 ligases control the cell surface abundance of GPCRs and other signaling receptors. - Source: PubMed
Publication date: 2026/05/26
Williams CarysNocka Laura MHedger GeorgeParashara PragyaPardon ElsLatorraca Naomi RPusapati Ganesh VSarkar ParijatLartey DorothyGao LeiMilenkovic LjiljanaChalk RodSteyaert JanMarqusee SusanCarrique LoïcBazan J FernandoRouse Sarah LKong Jennifer HSiebold ChristianRohatgi Rajat - Ferroptosis is one of the important mechanisms of secondary neuronal death after spinal cord injury (SCI). However, the upstream regulators that could be targeted for therapeutic intervention remain poorly defined. This study identifies gamma-glutamyl transferase 1 (GGT1) as a key driver of ferroptosis, upregulated in neurons post-SCI. Screening a 150-compound natural product library, we discovered Enocyanin (EA), which reduced GGT1 protein levels, protected neurons from hypoxic injury, and exhibited anti-ferroptotic effects. Mechanistically, EA promoted GGT1 degradation through the E3 ligase MGRN1, leading to K48-linked polyubiquitination and proteasomal clearance, halting ferroptosis. To improve EA's stability and delivery, we engineered a biomimetic nanoplatform (NSCm@EA) using neural stem cell membranes, enhancing drug accumulation at the injured spinal cord. At single-cell resolution, NSCm@EA was shown to precisely remodel neuronal subpopulations, selectively expanding γ-motor neurons and upregulating synaptic genes such as Gria2 and Negr1, while suppressing inflammatory and oxidative stress pathways. In summary, this study reveals GGT1's role in ferroptosis, identifies a natural product that induces its ubiquitin-mediated degradation, and presents a targeted biomimetic delivery strategy for precise intervention in spinal cord injury. - Source: PubMed
Publication date: 2026/05/14
Yang TaoYe LeiXie PeigenSong TaoChen JianZhao HengLiu ZhengshanChen XiDing JianingDing XintianShao AoWu MiaomiaoZhao FengdongTao SiyueYou Tao - Mahogunin Ring Finger 1 (MGRN1) is a multifunctional E3 ubiquitin ligase with broad biological significance and belongs to a small group of membrane-tethered E3s capable of regulating signaling receptors at the plasma membrane. Studies in mice first revealed its physiological importance, as loss of Mgrn1 leads to a wide range of phenotypes, including abnormal pigmentation, congenital malformations, and neurodegeneration. Remarkably, MGRN1 localizes to multiple cellular compartments, including the plasma membrane, mitochondria, nucleus, and endo-lysosomal pathway. MGRN1 is also involved in several cellular processes, including receptor regulation, protein homeostasis, and mitochondrial maintenance. While studies have emphasized the importance of MGRN1, it has been difficult to define unifying principles governing its function. In the present review, we summarize and integrate published findings to develop a clearer picture of MGRN1's roles, focusing on phenotypes observed in mouse models and the signaling pathways MGRN1 regulates. We propose shared mechanistic themes that reconcile the functional diversity of this unique E3 ligase, highlight gaps in the current literature, and identify areas for further investigation to better understand MGRN1's role in disease and evaluate its potential relevance for targeted protein degradation strategies. - Source: PubMed
Riglos AlyssaGunn Teresa MKong Jennifer H