Ask about this productRelated genes to: RUVBL2 antibody
- Gene:
- RUVBL2 NIH gene
- Name:
- RuvB like AAA ATPase 2
- Previous symbol:
- -
- Synonyms:
- RVB2, TIP48, TIP49b, Reptin52, ECP51, TIH2, INO80J, Rvb2
- Chromosome:
- 19q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 1999-09-07
- Date modifiied:
- 2016-03-07
Related products to: RUVBL2 antibody
Related articles to: RUVBL2 antibody
- PIWI proteins, a subfamily of the PAZ-PIWI domain (PPD) protein family, are traditionally regarded as germline factors that partner with PIWI-interacting RNAs (piRNAs) to silence transposons and regulate gene expression. However, growing evidence implicates PIWI proteins as oncogenic drivers in diverse somatic cancers, often acting through piRNA-independent mechanisms that remain incompletely understood. Here, we integrate transcriptomic, translatomic, and proteomic profiling of wild-type versus PIWIL1-knockout gastric cancer cells to uncover a non-canonical, translational role for PIWIL1, one of the four human PIWI proteins. We find that PIWIL1 selectively enhances the translation of 5'-terminal oligopyrimidine (TOP) mRNAs by activating mTOR complex 1 (mTORC1). Mechanistically, PIWIL1 interacts with the R2TP chaperone complex (RUVBL1-RUVBL2-RPAP3-PIH1D1) and promotes its association with TELO2, facilitating mTOR-RAPTOR assembly and mTORC1 activation. Functionally, PIWIL1 deficiency sensitizes gastric cancer cells to mTOR inhibition, and in clinical samples, PIWIL1 expression positively correlates with mTORC1 pathway activity. Together, these findings define a novel piRNA-independent mechanism through which PIWIL1 contributes to tumor progression, extend PIWI-mediated translational control from the germline to human cancers, and establish PIWIL1 as a potential therapeutic target for gastric cancer in synergy with mTOR inhibition. - Source: PubMed
Publication date: 2026/04/22
Fan TianquZhao JiangshaLi LingCui MeihuaZhang JiaweiChi TianShi Shuo - RuvB-like 1 (RUVBL1) and RuvB-like 2 (RUVBL2) are AAA ATPases that form hetero-oligomeric complexes involved in diverse cellular functions. Increasing evidence implicates the RUVBL1/2 complex as an essential cofactor of MYC, with RUVBL1/2 inhibition reducing c-MYC levels in vitro. Herein, we report a potent RUVBL1/2 inhibitor discovered through a Single-Molecule Tracking (SMT)-driven SAR campaign. Compared with a biochemical ADP-Glo assay, which exhibited limited dynamic range and poor reproducibility under our experimental conditions, the live-cell high-throughput RUVBL SMT assay provided robust and reproducible potency measurements and correlated strongly with cell viability and MYC degradation. Multiparameter optimization yielded compound 18, which demonstrated improved efficacy in a MYC-dependent Burkitt lymphoma xenograft model at a significantly lower dose than the RUVBL1/2 inhibitor CB-6644. This work establishes SMT as a powerful tool to facilitate the drug discovery SAR campaigns and evaluates the therapeutic potential of RUVBL1/2 inhibition in MYC-dependent cancers. - Source: PubMed
Publication date: 2026/04/22
Zheng LiPark EugeneLenihan JasonForrest William S RZhou XinFong CharmaineTang YangzhongKelly Marcus PDriouchi AmineTabatabaei AliWong HelenVargas Jesse DAlbright Samuel THoward ZacharySilva Maité BElliott Liam AFarley MichaelOrtega JoséJones StephenChang XiaoHeuer TaylorZheng QuanMorrison Huntly MBracho DanielDu QianLe JenniferTarafder AbhijitNawrocki GrzegorzSchyman PatricAkella LakshmiNguyen Mai KDing DaisyTao ArnoldPérez Fernando RodríguezVanBuren KaylaMalik RohitDumble MelissaAnderson Daniel JCleary LeahPiotrowski David WBeck Hilary P - The functional versatility of Hsp90 relies on its association with specialized co-chaperones that regulate client recruitment and maturation. Among these, the R2TP complex, comprising RUVBL1, RUVBL2, RPAP3 (Tah1 in yeast), and PIH1D1, acts as a conserved assembly factor essential for the biogenesis of large multiprotein machineries, including RNA polymerases, snoRNPs, PIKKs, and mTOR signaling complexes. RPAP3 functions as a central scaffold within the R2TP-Hsp90 system, linking Hsp90 and Hsp70 to the RUVBL1/2 ATPase core through its TPR domains and C-terminal interaction with PIH1D1. This modular organization enables RPAP3 to integrate chaperone-mediated folding with client delivery and complex assembly. Notably, dysregulation of RPAP3 has been implicated in oncogenic processes, highlighting its biomedical relevance. This review synthesizes current structural, functional, and evolutionary insights into RPAP3, focusing on its role within the R2TP-Hsp90 machinery and its emerging connections to human disease. - Source: PubMed
Publication date: 2026/04/09
Antonio Larissa MRamos Carlos H I - High-risk neuroblastoma is characterized by amplification and high or gene expression. These patients have a poor prognosis and there is an urgent need for more effective drugs. While strategies to develop inhibitors that directly target the MYC proteins have remained largely unsuccessful, recent preclinical studies have identified ATR, a key protein of the DNA damage response, as a promising alternative therapeutic target. Here, we identified a strong RUVBL1 and RUVBL2 signature in transcriptomics data derived from different -driven mice tumors treated with ATR inhibitors. The RUVBL proteins form a complex with ATPase activity that has broad cellular functions and we demonstrate that pharmacological inhibition of this protein complex results in a strong reduction of MYC(N) signaling, cell-cycle arrest, DNA damage, and apoptosis. We confirmed the association with and identified the genes as independent prognostic biomarkers in human primary neuroblastoma data. - Source: PubMed
Publication date: 2026/03/05
Siaw Joachim TettehClaeys ArneLai Wei-YunBorenäs MarcusHilgert ElienBekaert Sarah-LeeSanders EllenKaya IremVan Dorpe JoSpeleman FrankDurinck KaatHallberg BengtPalmer Ruth HVan den Eynden Jimmy - Postoperative delirium (POD) accelerates the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD) in elderly patients. Microglial metabolic reprogramming, a pivotal aspect of the immune-inflammatory response, modulates microglia-neuron interactions and postoperative cognitive function through microenvironmental alterations. Aberrant overexpression of RUVBL2 disrupts metabolic homeostasis, leading to stress granule (SG) aggregation and fibrosis. This study investigated the role of RUVBL2 in regulating metabolic reprogramming to mediate SG formation, with the aim of identifying novel prognostic targets for inhibiting glycolysis and mitigating POD-induced MCI progression. A POD model was established in aged MCI rats using 3% sevoflurane anesthesia for 3 h, combined with open reduction and internal fixation (ORIF). Multimodal magnetic resonance imaging (MRI) was employed to assess postoperative cognitive function. Glycolytic and oxidative phosphorylation (OXPHOS) activities in primary hippocampal microglia were quantified by extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Lentiviral-mediated RUVBL2 expression modulation was performed to verify its role in microglial metabolic reprogramming. Postoperative hippocampal microglia underwent metabolic reprogramming from OXPHOS to glycolysis, with RUVBL2 expression correlating positively with POD progression. Elevated RUVBL2 expression drove metabolic reprogramming, while RUVBL2 knockdown inhibited this process, alleviated pro-inflammatory microglia-induced neuroinflammation and SG aggregation, and improved spontaneous neural activity and hippocampus-dependent cognitive deficits. In primary hippocampal microglia, RUVBL2 knockdown enhanced OXPHOS-related OCR and reduced glycolysis-associated ECAR, producing a synergistic neuroprotective effect. These findings reveal the critical role of RUVBL2 in regulating POD, highlight metabolic reprogramming as a novel therapeutic target, and suggest RUVBL2 as a promising intervention strategy for POD. - Source: PubMed
Zhang LinWang ZixuanYang ChenyiWang XinyiLiu XingZhang HaonanLiu HuanLiao HuihuiChen JunWang Haiyun