Ask about this productRelated genes to: RNF126 antibody
- 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 antibody
Related articles to: RNF126 antibody
- Gliomas are highly invasive brain tumors in which metabolic reprogramming plays a pivotal role in tumor initiation and progression. METTL17, a mitochondria-associated methyltransferase, has been reported to enhance oxidative phosphorylation (OXPHOS) through mitochondrial RNA methylation; however, its function and regulatory mechanisms in glioma remain poorly understood. In this study, we manipulated METTL17 expression in primary P1 and U251 glioma cells using lentiviral-mediated knockdown and overexpression approaches. METTL17 depletion significantly suppressed cell proliferation, migration, and invasion, reduced ATP production and mitochondrial membrane potential, and increased reactive oxygen species accumulation, whereas METTL17 overexpression reversed these phenotypes. Mechanistically, METTL17 sustained mitochondrial OXPHOS by positively regulating key components of the electron transport chain, including NDUFA2, NDUFS1, SDHB, UQCRB, and MT-CO2. Mass spectrometry and co-immunoprecipitation analyses further revealed that METTL17 interacts with the E3 ubiquitin ligase RNF126, which destabilizes METTL17 through K116-dependent ubiquitination. Additionally, we demonstrate that SIRT5 acts as a desuccinylase for METTL17, removing succinylation at Lys274 and thereby facilitating RNF126-mediated ubiquitination and degradation of METTL17. In vivo xenograft experiments further validated that METTL17 knockdown markedly inhibited tumor growth and enhanced apoptosis. Collectively, these findings identify METTL17 as a critical regulator of mitochondrial function and energy metabolism in glioma and reveal a SIRT5-METTL17-RNF126 axis that governs METTL17 stability, providing new insights into glioma metabolic reprogramming and potential therapeutic targets. - Source: PubMed
Publication date: 2026/04/22
He ChunyanZhang ZixiaoWu XiaokeLin ChangjieJin JieyuNi YongQian YingfengWang Yin - DNA double-strand breaks generated during mitosis are thought to be inefficiently repaired, yet cellular responses to damage incurred specifically in late mitosis remain poorly understood. Here, we report that irradiation of cells synchronized in anaphase/telophase triggers partial DNA damage signaling, marked by H2AX phosphorylation and MDC1 accumulation. Consequently, cells enter G1 and S phases with unrepaired lesions. Proteomic analysis identified the E3 ubiquitin ligases RNF126 and BRAP as key regulators of this response, based on their selective ATM-dependent accumulation in irradiated late mitotic cells. Functional assays reveal that both proteins are required for damage-induced 53BP1 and RPA2 focus formation, resolution of DNA lesions, and survival after damage in late mitosis. Supporting their clinical relevance, both E3 ligases are overexpressed in selected tumors and associated with chromosomal instability. These findings suggest that RNF126 and BRAP help cells tolerate late mitotic damage and may represent potential vulnerabilities for improving genotoxic therapies in cancer. - Source: PubMed
Publication date: 2026/04/16
Ayra-Plasencia JesselJorge InmaculadaVázquez JesúsFreire RaimundoSmits Veronique A J - 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 -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: 2026/03/07
Modi AmanToriki Ethan SStieger Christian ELau Emily ASong ClaireChew AlyssaTsao AmyNishikawa KailaMcKenna JeffreyNomura Daniel K - The small GTPase Rab9 plays a major role in the vesicular trafficking of cation-independent mannose-6-phosphate receptor (CI-M6PR). CI-M6PR trafficking has also been reported to be perturbed by the dysfunction of a ubiquitin ligase necessary for protein quality control (PQC). However, the mechanism underlying the participation of the PQC machinery in CI-M6PR trafficking is poorly understood. In this study, we found an extremely short half-life of GDP-bound Rab9, which is in clear contrast to its phylogenetically closest relative, Rab7. Comparison of the amino acid sequences of these relatives revealed that hydrophobic residues are specifically exposed in the switch I region of Rab9a and that these residues are recognized by the PQC machinery. We defined this exposed hydrophobicity as a conformation-dependent hydrophobic (CDH) degron because its existence determines the instability of Rab proteins in a nucleotide-dependent manner. CDH degron-mediated instability is essential for Rab9a function, given that forced accumulation of CDH degron-mutated Rab9a in cells resulted in the defective localization of CI-M6PR, a similar phenotype observed in PQC dysfunction. Thus, the CDH degron-driven PQC system is necessary for the proper vesicular trafficking of CI-M6PR. We also identified valosin-containing protein/p97 as a CDH degron-dependent PQC factor for GDP-bound Rab9a. - Source: PubMed
Publication date: 2026/01/31
Shirai JunTakahashi ToshikiKawahara Hiroyuki - Midnolin (MIDN) is a newly recognized master regulator that drives ubiquitin-independent proteasomal degradation, yet the mechanisms governing its own turnover remain enigmatic. Here, we demonstrate that MIDN is ubiquitinated and identify RNF126 as the cognate E3 ligase. RNF126 physically associates with MIDN and catalyzes its ubiquitination, and mass spectrometry mapping reveals that this process occurs primarily at non-canonical cysteine, serine, and threonine residues (C230, C236, S237, T239, and S241) rather than at lysine residues. This non-classical ubiquitination targets MIDN for 26S-proteasomal degradation. dissection of the RNF126-MIDN axis shows that it governs EGR1 abundance and, consequently, the tumor-suppressor proteins PTEN and p53, thereby restraining the progression of testicular germ-cell tumors (TGCTs). Our findings reveal an unappreciated layer of MIDN regulation and identify the RNF126-MIDN ubiquitination cascade as a potential therapeutic vulnerability in TGCTs and related malignancies. - Source: PubMed
Publication date: 2026/01/07
Yang YunRen JinQiu XiangLiu YanlinYuan ShilinHu RongguiXia ZhixiongLi Chuanyin