Rnf126 siRNA_Lentivectors
- Known as:
- Rnf126 siRNA_Lentivectors
- Catalog number:
- i060978a
- Product Quantity:
- 500ng
- Category:
- -
- Supplier:
- ABM
- Gene target:
- Rnf126 siRNA_Lentivectors
Related genes to: Rnf126 siRNA_Lentivectors
- Gene:
- RNF126 NIH gene
- Name:
- ring finger protein 126
- Previous symbol:
- -
- Synonyms:
- FLJ20552
- Chromosome:
- 19p13.3
- Locus Type:
- gene with protein product
- Date approved:
- 2003-05-21
- Date modifiied:
- 2019-04-16
Related products to: Rnf126 siRNA_Lentivectors
Related articles to: Rnf126 siRNA_Lentivectors
- Molecular glue degraders represent a powerful modality for targeting proteins that are refractory to traditional inhibition. However, rational design principles for molecular glue degraders remain poorly defined. Previously, we reported a chemistry-centric strategy to identify covalent degradative handles that, when appended to established ligands, convert non-degradative inhibitors into molecular glue degraders by engaging permissive E3 ligases. This effort identified a fumarate-based electrophilic handle that covalently modified the E3 ligase RNF126, enabling degradation of multiple protein targets when transplanted across diverse ligands. Despite its conceptual impact, the high intrinsic reactivity and cytotoxicity of the fumarate handle limited its translational utility. Here, we report the development of an optimized and metabolically stabilized RNF126-targeting covalent handle incorporating a trans-cyclobutane linker that exhibits reduced glutathione reactivity and diminished cytotoxicity while retaining robust degradative activity. When appended to the BET bromodomain inhibitor JQ1, this optimized handle yielded a potent and selective BRD4 degrader whose activity was dependent on RNF126. Importantly, transplantation of this handle onto a previously non-inhibitory ligand targeting the androgen receptor (AR) and its truncation variant, AR-V7, enabled selective degradation of both AR and AR-V7 in androgen-independent prostate cancer cells, thereby robustly inhibiting AR transcriptional activity beyond the established AR antagonist enzalutamide. Collectively, these findings demonstrate an optimized RNF126-based covalent handle for the rational development of molecular glue degraders against transcriptional regulators, including undruggable variants such as AR-V7. - Source: PubMed
Publication date: 2026/07/23
Modi AmanToriki Ethan SStieger Christian ELau Emily ASong ClaireChew AlyssaTsao AmyNishikawa KailaMcKenna JeffreyNomura Daniel K - Bifunctional soluble epoxide hydrolase (sEH) represents an attractive therapeutic target for inflammation-associated disorders. Targeted protein degradation (TPD) offers new opportunities for targeting and blocking the enzymatic function of sEH, thereby ameliorating inflammation-related diseases. Herein, a diversity-oriented synthesis of 24 proteolysis-targeting chimeras (PROTACs) and 5 hydrophobic tag-targeted degraders (HyTTDs) was successfully facilitated by a Ugi-4CR reaction. Notably, the E3 ubiquitin ligase RNF126 and hydrophobic tag (HyT) ligands are delicately embedded in the degraders and exhibit moderate to good degradative activities toward sEH. After comprehensive biological screening, the PROTAC molecule was found to have the highest degradation potency (DC = 2.9 nM) and exhibited satisfactory degradative pharmacokinetic properties within 6 h, which further proved to significantly attenuate LPS-induced acute inflammation, highlighting its therapeutic utility. - Source: PubMed
Publication date: 2026/07/17
Yin ChenxinBai YingLi ChunxiangYang EnqinYin Hou-HuaMorisseau ChristophePan Qing-JinDai PingHuang LingHammock Bruce DNie ShenyouHe YiLiu Jun-Yan - Ring finger protein 126 (RNF126) is a RING-type E3 ubiquitin ligase that has recently emerged as a multifaceted regulator of cellular homeostasis, stress adaptation, and disease progression. Through its structurally distinct zinc-finger and catalytic RING domains, RNF126 orchestrates substrate recognition and ubiquitin transfer, generating diverse ubiquitin linkages with both proteolytic and nonproteolytic functions. Initially characterized as a component of the protein quality control (PQC) machinery, RNF126 cooperates with chaperones such as BAG6 and UBQLN1 to eliminate mislocalized and misfolded proteins, thereby maintaining proteostasis. Beyond PQC, RNF126 plays pivotal roles in DNA damage response pathways by regulating homologous recombination, non-homologous end joining, checkpoint signaling, and genome stability through substrates, including MRE11, Ku80, RNF168, and 14-3-3σ. Genetic studies have further demonstrated its importance in embryogenesis and male fertility, and accumulating evidence has identified RNF126 as a critical driver of malignancy in multiple cancers. RNF126 promotes tumor progression by degrading or modulating key regulators, such as p21, PTEN, p53, PDKs, and LKB1, thereby enhancing proliferation, metabolic reprogramming, anoikis resistance, metastasis, and chemo/radioresistance. Intriguingly, RNF126 exhibits context-dependent functions, acting as an oncogene or tumor suppressor depending on the tissue type and substrate selection. In addition to cancer, RNF126 has been implicated in neurodegeneration, cardiac pathology, antiviral immunity and adaptive immune regulation. This review summarizes the current knowledge of RNF126 structure, ubiquitin signaling mechanisms, physiological functions, and pathological roles, while discussing emerging therapeutic strategies and future challenges for targeting RNF126 in precision medicine. - Source: PubMed
Publication date: 2026/06/25
Vu Anh DucMori ShioriSakamoto Takeharu - The mechanistic target of rapamycin complex 1 (mTORC1) serves as a central metabolic hub that integrates nutrient signals and orchestrates cellular metabolism to regulate many fundamental cell processes. While mTORC1 activation is known to occur both on lysosomal membranes and at the Golgi apparatus in response to environmental cues, the molecular mechanisms governing its Golgi-associated activation remain poorly understood. In this study, we identified YIF1A as a novel Golgi-localized regulator of growth factor-mediated mTORC1 signaling. Mechanistically, YIF1A interacted with the E3 ubiquitin ligase RNF126 to facilitate K48-linked polyubiquitination of G3BP1/2, thereby promoting mTORC1 activation. Genetic depletion of either YIF1A or RNF126 stabilized G3BP1/2 proteins and significantly impaired mTORC1 activity. Notably, YIF1A knockdown conferred resistance to etoposide- and doxorubicin-induced cellular senescence. The evolutionary conservation of this pathway was demonstrated by extended or shortened lifespan in Caenorhabditis elegans lacking or overexpressing yif-1, the invertebrate ortholog of YIF1A. Our findings not only elucidate a previously unrecognized Golgi-specific regulatory axis for mTORC1 activation but also suggest YIF1A as a potential therapeutic target for modulating aging-related pathologies. - Source: PubMed
Publication date: 2026/06/23
Zhang XiaogangLiu LuyingShang MengdiHu BinZhu ShuWang XiLiu JieyingHan YanchunWei XiaodanCao QiLi FanGao LijieSun JingyuYu JiaqiTan ChentaiDong MenghuaTang Tie-ShanWang Jiu-Qiang - Fetal growth restriction (FGR) remains a major contributor to neonatal morbidity and mortality worldwide, with limited effective diagnostic and therapeutic options. To better understand its molecular mechanism, we performed integrated multi-omics analyses of placental tissues from FGR pregnancies and normal controls, identifying Ring Finger Protein 126 (RNF126), an E3 ubiquitin ligase, as a key regulator of FGR and a potential biomarker distinguishing FGR from small-for-gestational-age (SGA) fetuses. Placenta-specific RNF126 conditional knockout (cKO) mice demonstrated a causal role of elevated placental RNF126 in FGR development . Functional studies revealed that RNF126 induced endoplasmic reticulum (ER) stress and apoptosis in trophoblasts. Mechanistically, RNF126 promoted a ubiquitin-proteasome-mediated degradation of the MYH9/MYH10 complex, thereby exacerbating ER stress and impairing trophoblast function, with lysine 833 (K833) of MYH9 identified as a critical ubiquitination site. Collectively, these findings elucidate an RNF126-mediated pathogenic mechanism in FGR and highlight RNF126 as a promising biomarker and therapeutic target. - Source: PubMed
Publication date: 2026/06/08
Lu LilinYe XiaomeiLan JiawenXu ShuxiuCheng ManyuLv ChenlinZhou JunLi Jing