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
- DNA double-strand breaks (DSBs) are among the most cytotoxic forms of chromosomal lesions and are primarily repaired through homologous recombination (HR) or non-homologous end joining (NHEJ). The precise repair of DSBs via HR necessitates 5'-3' end resection to generate 3'-single-stranded DNA (ssDNA) overhangs, which function as templates for repair synthesis. However, the proteins involved in HR, particularly those acting in the critical early stages preceding DNA end resection, and their regulatory mechanisms in response to ionizing radiation (IR), remain incompletely characterized. In this study, we identify the nuclear receptor co-activator NCOA4 as a novel DNA damage responsive protein. We demonstrate that this protein is recruited to sites of DNA damage and is enriched during the S/G2 phase of the cell cycle. Immunofluorescence and reporter gene assays demonstrate that depletion of NCOA4 reduces the IR-induced foci formation of RAD51 and RPA2 and impairs HR efficiency. Mechanistically, NCOA4 interacts with the AAA + ATPases RUVBL1/2, and depletion of RUVBL1/2 has been shown to reduce the recruitment of NCOA4 at DNA damage sites. The knockdown of RUVBL1 or RUVBL2 phenocopies NCOA4 deficiency, and simultaneous knockdown of RUVBL1/2 and NCOA4 does not further reduce the RPA2 RIF, confirming that the entire NCOA4-RUVBL1/2 complex acts together to promote HR. Furthermore, depletion of NCOA4 has been shown to sensitize cancer cells to radiotherapy in tumor-bearing nude mouse models. Consequently, the present findings indicate that the NCOA4-RUVBL1/2 axis is capable of recognizing DNA double-strand breaks and promoting the homologous recombination repair pathway, thereby contributing to the maintenance of genomic integrity. This process may potentially play a role in modulating radioresistance in malignant tumors and expanding the landscape of therapeutic targets. - Source: PubMed
Publication date: 2026/06/09
Chen YingyingZhang QiTao ZongjianLv ShaotingQuan ChengZhou GangqiaoChen Hongxia - The R2TP chaperone complex comprises two AAA+ proteins, RUVBL1 and RUVBL2, along with RPAP3 and PIH1D1. R2TP functions in concert with other chaperones, such as HSP90 and HSP70, to facilitate the assembly of macromolecular complexes integral to the regulation of cell growth and proliferation. Moreover, several adaptors interact with R2TP to impart substrate specificity. Nevertheless, the precise mechanism underlying R2TP-mediated complex assembly remains unknown. This review summarizes the current knowledge regarding R2TP's involvement in the assembly, stabilization, and activity of multiple protein complexes, including box C/D and H/ACA small nucleolar ribonucleoproteins (snoRNPs), spliceosome small nuclear ribonucleoproteins (snRNPs), the tuberous sclerosis complex (TSC) , axonemal dynein arms, RNA polymerases, phosphatidylinositol 3-kinase-related kinases (PIKK), and the MRE11-RAD50-NBS1 (MRN) complex. Additionally, the role of R2TP in ciliogenesis, circadian rhythm regulation, and transcriptional condensate formation is discussed. Finally, the latest structural studies pertaining to R2TP and its related complexes are examined. - Source: PubMed
Publication date: 2026/06/04
Mohamed MaryamaWu RuikaiHoury Walid A - Cutaneous melanoma (SKCM) is a highly aggressive malignant tumor of the skin, characterized by rapid progression, strong metastatic potential, and poor clinical prognosis, which poses a serious threat to human health and imposes a heavy burden on global healthcare systems. Despite significant advances in therapeutic strategies such as targeted therapy and immunotherapy in recent years, the clinical outcomes of SKCM patients remain suboptimal, highlighting the urgent need to identify novel molecular biomarkers and therapeutic targets that can facilitate early diagnosis, accurate prognosis evaluation, and effective treatment of this disease. RUVBL2, a member of the AAA+ ATPase family, has been increasingly recognized as a key regulator in tumorigenesis and progression. Accumulating evidence from previous studies has demonstrated that RUVBL2 exerts oncogenic effects in multiple human malignancies. For instance, knockdown of RUVBL2 can inhibit cell proliferation, promote apoptosis, induce senescence, and suppress migration in hepatocellular carcinoma, and its high expression is closely associated with poor prognosis and chemoresistance. In colorectal cancer, RUVBL2 mRNA modified by m6A can be recognized and bound by YTHDF1 to enhance translation initiation and protein expression, and depletion of RUVBL2 impairs YTHDF1-driven oncogenic translation, leading to cell cycle arrest and apoptosis. Additionally, RUVBL2 has been shown to participate in the regulation of oncogenic signaling pathways, immune evasion, and therapeutic sensitivity in pancreatic cancer, bladder cancer, and breast cancer. However, the expression pattern of RUVBL2 in SKCM, its correlation with clinical prognosis and tumor immune microenvironment, as well as its potential functional role in SKCM progression, have not been fully elucidated to date. In view of the critical role of immune cell infiltration in the pathogenesis and progression of SKCM, and the clinical significance of immune checkpoint inhibitors (e.g., anti-PD-1 and anti-CTLA-4 agents) in SKCM treatment, exploring the association between RUVBL2 and tumor immune infiltration, as well as its predictive value for immunotherapeutic efficacy, is of great importance. Therefore, the present study aims to systematically investigate the expression level of RUVBL2 in SKCM and its correlation with clinical prognosis by integrating public database resources (TCGA, GTEx, and HPA) and in vitro experimental validation. Furthermore, we intend to explore the functional role of RUVBL2 in regulating SKCM cell proliferation, migration, invasion, and apoptosis, and clarify its association with immune cell infiltration and sensitivity to immunotherapy. The findings of this study are expected to provide a theoretical basis for the development of novel diagnostic markers and therapeutic strategies for SKCM. - Source: PubMed
Publication date: 2026/05/26
Zhang YigangGao MengruQu XiangyuCui LeiWu JunjunDeng Jiabin - 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
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