| 1997 |
RUVBL1 (TIP49/TIP49a) was identified as a TBP-interacting protein that co-immunoprecipitates with TBP in a nuclear complex, and its sequence contains Walker A and B motifs homologous to bacterial RuvB, suggesting ATPase/helicase activity. |
Affinity purification with histidine-tagged TBP, immunoprecipitation, sequence analysis |
Biochemical and biophysical research communications |
Medium |
9196036
|
| 1998 |
RUVBL1 (Pontin52) was identified as a nuclear protein that binds beta-catenin at Armadillo repeats 2-5 and also binds the TATA-box binding protein (TBP), forming an in vivo multiprotein complex with beta-catenin and LEF-1/TCF, implicating RUVBL1 in beta-catenin-mediated nuclear transactivation. |
Yeast two-hybrid, co-immunoprecipitation, GST pulldown |
Proceedings of the National Academy of Sciences of the United States of America |
High |
9843967
|
| 1998 |
RUVBL1 is an essential gene; yeast null mutants of the RUVBL1 homolog (scRUVBL1) are nonviable. RUVBL1 was co-immunoprecipitated with at least three other cellular proteins and was detected in the RNA polymerase II holoenzyme complex. |
Yeast two-hybrid (identification with RPA3 as bait), co-immunoprecipitation, yeast null mutant viability assay |
The Journal of biological chemistry |
High |
9774387
|
| 1999 |
RUVBL1 (TIP49a/TIP49) possesses ATPase activity stimulated by single-stranded DNA and ATP-dependent DNA helicase activity with 3'-to-5' directionality, as demonstrated with recombinant purified protein. |
In vitro ATPase assay, DNA helicase assay, UV cross-linking assay with purified recombinant protein |
The Journal of biological chemistry |
High |
10336418
|
| 1999 |
RUVBL2 (TIP49b) forms a physical complex with RUVBL1 (TIP49a) in a ~700 kDa cellular complex, has ATPase activity stimulated by single-stranded DNA, and ATP-dependent DNA helicase activity with 5'-to-3' directionality (opposite polarity to RUVBL1). Both genes are essential in S. cerevisiae. |
Co-immunoprecipitation, in vitro ATPase and helicase assays, yeast genetic complementation |
The Journal of biological chemistry |
High |
10428817
|
| 2000 |
RUVBL1 (Pontin52) and its homolog RUVBL2 (Reptin52) function as antagonistic regulators of beta-catenin/TCF transcriptional activity: RUVBL1 activates while RUVBL2 represses Wnt target gene transcription, and this antagonism is evolutionarily conserved in Drosophila (dpontin/dreptin). |
Reporter gene assays, co-immunoprecipitation, Drosophila genetic experiments (Wingless signaling) |
The EMBO journal |
High |
11080158
|
| 2001 |
RUVBL1 (TIP49a) functions as a plasminogen-binding protein on the U937 cell surface, with a C-terminal lysine mediating plasminogen binding (Kd ~0.57 μM) and enhancing plasminogen activation ~8-fold. |
Protein purification, carboxypeptidase B treatment, ligand blotting with 125I-plasminogen, plasminogen activation assay |
The Journal of biological chemistry |
Medium |
11027681
|
| 2002 |
RUVBL1 (TIP49) binds the E2F1 transactivation domain and modulates both E2F1-mediated transformation and apoptosis, while also being required for c-Myc-mediated apoptosis (unlike TRRAP which does not affect apoptosis). |
Co-immunoprecipitation, dominant-negative overexpression, apoptosis assays |
Oncogene |
Medium |
12185582
|
| 2003 |
RUVBL1 (TIP49) ATPase activity is required for beta-catenin-mediated neoplastic transformation and TCF-dependent gene activation. RUVBL1 was found in complexes with chromatin-remodeling and histone-modifying factors including TIP60, TRRAP, and BAF53, and chromatin immunoprecipitation showed RUVBL1, TIP60, and TRRAP occupying the ITF-2 promoter; RUVBL1 ATPase-dead mutant decreased histone acetylation at TCF-binding sites. |
ATPase-deficient mutant (D302N), siRNA knockdown, reporter gene assay, co-immunoprecipitation, chromatin immunoprecipitation |
Cancer research |
High |
14695187
|
| 2003 |
RUVBL1 associates with alpha- and gamma-tubulin, localizes to the centrosome and mitotic spindle during mitosis in a stage-dependent manner (metaphase: centrosome and astral microtubules; anaphase B: polar tubule interdigitation zone), and promotes in vitro tubulin assembly. |
Protein affinity chromatography, co-immunoprecipitation, confocal immunofluorescence microscopy, in vitro tubulin assembly assay |
Cell motility and the cytoskeleton |
Medium |
14506706
|
| 2003 |
RUVBL1 (Pontin52/TIP49a) promotes COX-2 expression in colon cancer cells and co-localizes with LEF-1 at the COX-2 promoter, linking RUVBL1 to Wnt-pathway-dependent gene regulation. |
Overexpression, siRNA knockdown, reporter assay |
Molecular cancer |
Low |
14675489
|
| 2005 |
Drosophila Pont (Pontin/RUVBL1 ortholog) physically binds dMyc and shows strong dominant genetic interaction with dmyc in controlling tissue growth, cell competition, and repression of specific target genes (e.g., mfas). |
Co-immunoprecipitation, genetic interaction analysis, mitotic clone analysis in Drosophila |
Proceedings of the National Academy of Sciences of the United States of America |
High |
16087886
|
| 2006 |
Crystal structure of human RuvBL1 hexamer at 2.2 Å resolution revealed three domains: domains I and III involved in ATP binding/hydrolysis, and domain II (unique among AAA+ proteins, absent from bacterial RuvB) functioning as a novel DNA/RNA-binding domain. RuvBL1 binds single-stranded DNA/RNA and double-stranded DNA, but only marginal ATPase activity was detected with purified protein alone, suggesting requirement for cofactors. |
X-ray crystallography (2.2 Å), DNA binding assays, ATPase assay |
The Journal of biological chemistry |
High |
17060327
|
| 2006 |
The human TIP48/TIP49 (RUVBL2/RUVBL1) complex forms a dodecameric double-ring structure (as shown by electron microscopy 3D reconstruction at 20 Å), with synergistic ATPase activity requiring both subunits; no DNA helicase or branch migration activity was detected for the isolated complex in vitro. |
Electron microscopy 3D reconstruction, ATPase assay, DNA helicase assay, catalytic mutant analysis |
Journal of molecular biology |
High |
17157868
|
| 2008 |
Human RUVBL1 (Rvb1) is required for the histone acetyltransferase (HAT) activity of the Tip60/NuA4 complex. Depletion of RUVBL1 increases persistence of phospho-H2AX after DNA damage without increasing DNA damage itself. The mechanism involves RUVBL1 maintaining Tip60 HAT activity, which acetylates histone H4, enabling subsequent dephosphorylation of phospho-H2AX. |
siRNA knockdown, HAT activity assay, γH2AX immunofluorescence, histone H4 acetylation assay |
Molecular and cellular biology |
High |
18285460
|
| 2008 |
RUVBL1 (TIP49) depletion reduces RAD51 recruitment to chromatin and nuclear foci formation (~50% reduction) after double-strand breaks and interstrand crosslinks, without affecting H2AX phosphorylation or checkpoint signaling; this reduction is rescued by HDAC inhibitor treatment, linking RUVBL1-mediated chromatin modification to homologous recombination. |
siRNA knockdown, immunofluorescence for RAD51 foci, chromatin fractionation |
The international journal of biochemistry & cell biology |
Medium |
18834951
|
| 2008 |
Yeast Rvb1 and Rvb2 form a heterohexameric ring (not double-hexamer) with enhanced ATPase activity relative to individual proteins, further stimulated by dsDNA with 5' or 3' overhangs, and exhibit 5'-to-3' DNA helicase activity. |
Electron microscopy, in vitro ATPase assay, DNA helicase assay, analytical ultracentrifugation |
Journal of molecular biology |
High |
18234224
|
| 2009 |
TIP48 (RUVBL2) and TIP49 (RUVBL1) play a major role in catalyzing H2A.Z exchange into nucleosomes via their ATPase activities, acting cooperatively with TIP60-mediated acetylation of nucleosomal H2A, which specifically facilitates small complex-mediated H2A.Z exchange. |
Biochemical purification of H2A.Z-interacting complexes, in vitro H2A.Z exchange assay, ATPase activity assay |
Nucleic acids research |
High |
19696079
|
| 2010 |
RUVBL1 and RUVBL2 associate with each PIKK family member (including SMG-1, ATM, ATR, mTOR, DNA-PKcs, TRRAP), control PIKK mRNA abundance upon knockdown, and promote formation of mRNA surveillance complexes during nonsense-mediated mRNA decay (NMD) by associating with SMG-1 and mRNPs in the cytoplasm. |
Co-immunoprecipitation, siRNA knockdown, NMD reporter assays, RNA immunoprecipitation |
Science signaling |
High |
20371770
|
| 2011 |
RUVBL1 (TIP49) represses p53 transcription by binding the p53 promoter, interfering with RNF20/hBRE1-mediated histone H2B monoubiquitination and promoting PAF1-mediated histone H3K9 trimethylation, thereby blocking p53-mediated apoptosis. EHF directly activates RUVBL1 transcription. |
ChIP, reporter gene assay, co-immunoprecipitation, siRNA knockdown, apoptosis assay |
EMBO reports |
Medium |
21617703
|
| 2011 |
Hsp90 forms complexes with RUVBL1/2 and the Tel2 complex, and Hsp90 inhibition reduces levels of all PIKK family members and suppresses PIKK-mediated signaling, suggesting Hsp90, RUVBL1/2, and Tel2 form a joint regulatory complex for PIKK stability. |
Co-immunoprecipitation, Hsp90 inhibitor treatment, Western blot for PIKK levels |
Cancer science |
Medium |
21951644
|
| 2011 |
Crystal structure of RuvBL1-RuvBL2 complex with truncated domain II revealed a dodecamer of two heterohexameric rings with alternating RuvBL1 and RuvBL2 monomers bound to ADP/ATP, interacting via retained domain II. Truncation of domain II increased ATP consumption substantially. Domain II auto-inhibits DNA unwinding activity of the human RuvBL proteins. |
X-ray crystallography, small-angle X-ray scattering, ATPase assay, DNA helicase assay |
Journal of structural biology |
High |
21933716
|
| 2012 |
Cryo-EM structures of human double-ring RuvBL1-RuvBL2 complexes revealed two coexisting conformations (compact and stretched), driven by movements in DII domains. These conformational transitions expose/conceal DNA-binding regions, providing a mechanism linking DII dynamics to regulation of nucleic acid binding. |
Cryo-electron microscopy, image classification |
Nucleic acids research |
High |
23002137
|
| 2012 |
The TTT-RUVBL1/2 complex responds to the cell's metabolic state (ATP levels from glucose/glutamine metabolism), is disassembled upon energy depletion, and is required for mTORC1 assembly as obligate dimers, for mTORC1-Rag interaction, and for lysosomal localization of mTORC1, acting via an AMPK-, TSC1/2-, and Rag-independent mechanism. |
Co-immunoprecipitation, siRNA knockdown, mTORC1 activity assays, lysosomal fractionation, metabolic perturbation |
Molecular cell |
High |
23142078
|
| 2012 |
Crystal structure of TIP49b (RUVBL2) hexamer and molecular dynamics simulations established that domain mobility affects ATPase activity, and hexamerization itself downregulates ATPase activity. A three-amino acid insertion in the lik-TIP49b mutant remotely affects the ATP-binding/hydrolysis pocket by altering conformational dynamics, uncoupling ATP hydrolysis from DNA binding. |
X-ray crystallography, molecular dynamics simulation, ATPase assay |
Structure |
High |
22748767
|
| 2013 |
RuvbL1 and RuvbL2 associate with the aggresome, act as protein disaggregases: polypeptides with unfolded structures and amyloid fibrils stimulate their ATPase activity, and RuvbL complexes actively disassemble protein aggregates. The aggresome substrate synphilin-1 interacts directly with the RuvbL1 barrel-like structure near the central channel opening. |
siRNA knockdown, aggresome formation assay, ATPase activity assay, protein disaggregation assay, direct protein interaction assay |
The EMBO journal |
High |
26303906
|
| 2014 |
YY1 oligomers bind RuvBL1-RuvBL2 hetero-oligomeric complexes preferentially through RuvBL1. DNA binding by YY1 oligomers is enhanced by RuvBL1-RuvBL2, and the ATPase activity of RuvBL2 and YY1 are both required for RAD51 foci formation during homologous recombination. |
Electron microscopy, pulldown, co-immunoprecipitation, bimolecular fluorescence complementation, RAD51 foci assay, ATPase-deficient mutants |
The Journal of biological chemistry |
Medium |
24990942
|
| 2014 |
RuvBL1 and RuvBL2 co-purify with the Fanconi anemia (FA) core complex under native conditions. Depletion of RuvBL1-RuvBL2 causes hallmark FA phenotypes (crosslinker sensitivity, chromosomal instability, defective FA pathway activation) and reduces FA core complex abundance in human cells. Genetic knockout of RuvBL1 in mice is embryonic lethal; conditional hematopoietic KO causes aplastic anemia. |
Native complex purification and mass spectrometry, siRNA depletion, crosslinker sensitivity assay, conditional mouse KO |
Nucleic acids research |
High |
25428364
|
| 2014 |
Cytoplasmic RUVBL1 directly binds filamentous actin (F-actin) in cell protrusions, increases local G-actin concentration, promotes peripheral actin polymerization, and thereby induces formation of membrane protrusions that enhance pancreatic cancer cell invasion. |
siRNA knockdown, co-immunoprecipitation with actin, confocal immunofluorescence, invasion assay |
International journal of oncology |
Medium |
24728183
|
| 2015 |
RUVBL1 localizes to structures of the mitotic spindle apparatus in anaphase-to-telophase, partially co-localizing with PLK1. PLK1 phosphorylates RUVBL1 (but not RUVBL2) in vitro and physically associates with RUVBL1 in vivo. siRNA knockdown of RUVBL1 or RUVBL2 causes severe chromosome misalignment and missegregation. RUVBL1 ATPase activity is indispensable for cell proliferation. |
Immunofluorescence microscopy, in vitro kinase assay (PLK1 on RUVBL1), co-immunoprecipitation, siRNA knockdown, ATPase-deficient mutant |
PloS one |
High |
26201077
|
| 2015 |
ECD (Ecdysoneless) protein directly interacts with RUVBL1 component of the R2TP co-chaperone complex in a phosphorylation-independent manner (distinct from PIH1D1 interaction), and this RUVBL1-ECD interaction is essential for ECD's cell cycle progression function. |
Co-immunoprecipitation, GST pulldown, phosphorylation mutant analysis, cell cycle rescue assay |
Molecular and cellular biology |
Medium |
26711270
|
| 2017 |
PRMT5 methylates RUVBL1 at arginine R205, which is required for TIP60-dependent histone H4K16 acetylation, 53BP1 displacement from DNA double-strand breaks, and promotion of homologous recombination. RUVBL1 methylation by PRMT5 is critically required for TIP60 acetyltransferase activity but does not affect ATM activation by TIP60. |
In vitro methylation assay (PRMT5 on RUVBL1), HAT activity assay, ChIP, immunofluorescence for 53BP1/RAD51 foci, site-directed mutagenesis (R205A) |
Molecular cell |
High |
28238654
|
| 2017 |
An Ino80 ATPase domain (Ino80INS) stimulates yeast Rvb1/Rvb2 ATPase activity by 16-fold while promoting dodecamerization of the Rvbs. Ino80INS binds asymmetrically along the dodecamerization interface, resulting in a conformationally flexible dodecamer that collapses into hexamers upon ATP addition, demonstrating chaperone-like protein assembly behavior. |
In vitro ATPase assay, cryo-EM, mass spectrometry, integrative structural modeling |
Cell reports |
High |
28591576
|
| 2017 |
RUVBL1-RUVBL2 directly interacts with ZNHIT2 to mediate R2TP/Prefoldin-like complex association with U5 snRNP; the zinc-finger HIT domain of ZNHIT2 binds RUVBL2. Disruption of ZNHIT2 and RUVBL2 expression impacts U5 snRNP protein composition, suggesting R2TP/PFDL promotes U5 snRNP assembly. |
Affinity purification-mass spectrometry, co-immunoprecipitation, siRNA knockdown, native PAGE analysis of snRNP composition |
Nature communications |
High |
28561026
|
| 2017 |
Adenovirus E1A suppresses type I interferon-stimulated gene expression by binding to RUVBL1 via its C-terminus and being recruited to RUVBL1-regulated promoters in an interferon-dependent manner, thereby preventing their activation. |
Co-immunoprecipitation (E1A-RUVBL1), ChIP, reporter gene assay, siRNA knockdown of RUVBL1 |
Journal of virology |
Medium |
28122980
|
| 2018 |
RUVBL1 interacts with DNAAF1 (dynein arm assembly factor) and IFT88 (intraflagellar transport protein); loss of RUVBL1 perturbs co-localization of DNAAF1 with IFT88. RUVBL1 orthologs show asymmetric left-sided distribution at the mouse embryonic node and zebrafish Kupffer's vesicle (dependent on DNAAF1), linking RUVBL1 to symmetry breaking and cardiac development. |
Co-immunoprecipitation, co-localization imaging, siRNA knockdown, zebrafish complementation assay |
Human molecular genetics |
Medium |
29228333
|
| 2018 |
Conditional deletion of Ruvbl1 in renal tubular epithelial cells causes renal failure with tubular dilatations and fewer ciliated cells. Inducible deletion in cells with motile cilia causes hydrocephalus. Cilia of Ruvbl1-negative cells lack crucial ciliary proteins, consistent with RUVBL1-dependent cytoplasmic pre-assembly of ciliary protein complexes. |
Conditional mouse knockout, histology, immunofluorescence |
Experimental & molecular medicine |
High |
29959317
|
| 2018 |
RUVBL1 activates the RAF/MEK/ERK pathway by binding C-RAF and inhibiting phosphorylation of C-RAF at serine 259, thereby promoting lung cancer cell proliferation and invasion. |
Co-immunoprecipitation (RUVBL1-C-RAF), Western blot for pS259-C-RAF, siRNA/CRISPR knockout, xenograft tumor model |
Biochemical and biophysical research communications |
Medium |
29545175
|
| 2019 |
CB-6644, an allosteric small-molecule inhibitor of RUVBL1/2 ATPase activity, specifically engages RUVBL1/2 in cancer cells. Drug-resistant cell clones contain amino acid mutations in RUVBL1 or RUVBL2, confirming on-target cell killing. CB-6644 significantly reduces tumor growth in AML and multiple myeloma xenograft models. |
ATPase activity assay, resistance mutation mapping, xenograft mouse models |
ACS chemical biology |
High |
30640450
|
| 2019 |
Cryo-EM structures of the human R2TP complex (RUVBL1-RUVBL2-RPAP3-PIH1D1) revealed that PIH1D1 binding to the DII domain of RUVBL2 induces conformational rearrangements that destabilize an N-terminal segment of RUVBL2 acting as a gatekeeper to nucleotide exchange, thereby regulating ATPase activity of the complex. |
Cryo-EM structural analysis |
Science advances |
High |
31049401
|
| 2019 |
RUVBL1/2 ATPase activity is necessary for maturation or dissociation of the PAQosome (large RUVBL1/2-dependent multiprotein complex) and for DNA replication; inhibition of ATPase activity causes S-phase arrest and replication catastrophe in cancer cells. |
ATPase inhibitor (CB-6644) treatment, flow cytometry (S-phase arrest), native PAGE (PAQosome integrity) |
Cell chemical biology |
High |
31883965
|
| 2019 |
RUVBL1 recruits to the Tip60 complex, and the RUVBL1-β-catenin/LEF1-TIP60 complex promotes histone H4K16 acetylation near the C-myc promoter, enhancing chromatin remodeling and transcriptional activity. |
Co-immunoprecipitation, chromatin immunoprecipitation, histone H4K16Ac assay, shRNA knockdown |
Molecular cancer |
Medium |
31665067
|
| 2020 |
DHX34, an RNA helicase regulating NMD initiation, directly interacts with RUVBL1-RUVBL2. Cryo-EM shows DHX34 induces extensive changes in the N-termini of every RUVBL2 subunit, stabilizing a conformation that does not bind nucleotide and thereby down-regulates ATP hydrolysis; DHX34 acts exclusively on RUVBL2 subunits. This couples RUVBL ATPase activity to NMD initiation complex assembly. |
Cryo-EM, in vitro binding assay, ATPase assay, ATPase-deficient mutants, co-immunoprecipitation |
eLife |
High |
33205750
|
| 2020 |
RUVBL1-RUVBL2 complex controls assembly and composition of the γ-tubulin ring complex (γTuRC) in human cells; RUVBL interacts with γTuRC subcomplexes but is not part of fully assembled γTuRC. In a heterologous coexpression system, RUVBL can assemble γTuRC from minimal core subunits; reconstituted γTuRC has nucleation activity. |
siRNA knockdown, coexpression reconstitution, cryo-EM (γTuRC structure at ~4.0 Å), microtubule nucleation assay, co-immunoprecipitation |
Science advances |
High |
33355144
|
| 2020 |
Both overexpression and depletion of RUVBL1 impede DNA replication fork rates and cause accumulation of phospho-H2AX in a transcription-dependent manner. RUVBL1 overexpression enhances c-Myc-dependent RNAPII pause release and increases global transcription; RUVBL1 depletion increases ubiquitination of RNAPII (Rpb1) and reduces its chromatin mobility, indicating stalled RNAPII. |
DNA fiber assay (replication fork rate), γH2AX immunofluorescence, RNAPII ChIP (phospho-Ser2 CTD), transcription inhibition rescue |
The international journal of biochemistry & cell biology |
Medium |
32846207
|
| 2021 |
NOPCHAP1 (C12ORF45) acts as a bridge between NOP58 and the PAQosome: it makes direct physical interactions with the CC-NOP domain of NOP58 and domain II of RUVBL1/2 AAA+ ATPases. NOPCHAP1 interaction with RUVBL1/2 is disrupted upon ATP binding. NOPCHAP1 KO cells show decreased NOP58 expression, establishing NOPCHAP1 as a client-loading cofactor selecting NOP58 for RUVBL1/2-mediated box C/D snoRNP assembly. |
Co-immunoprecipitation, NOP58 mutant analysis, mass spectrometry proteomics, KO cell analysis |
Nucleic acids research |
High |
33367824
|
| 2021 |
RUVBL1 interacts with SMCHD1 and is present at D4Z4 chromatin in myocytes; loss of RUVBL1 further derepresses DUX4 expression in FSHD myocytes, establishing RUVBL1 as a functional component of SMCHD1-mediated D4Z4 chromatin repression. |
Quantitative proteomics (SMCHD1 pulldown), ChIP-seq, siRNA knockdown, DUX4 expression assay |
Scientific reports |
Medium |
34880314
|
| 2021 |
RUVBL1/2 inhibition significantly reduces histone H3K4me3 at promoters of pro-inflammatory genes (Nos2, Il6) and diminishes NF-κB recruitment to corresponding enhancers, establishing RUVBL1/2 as regulators of macrophage pro-inflammatory responses via epigenetic (H3K4me3) mechanisms. |
siRNA knockdown, pharmacological inhibition (CB-6644), ChIP for H3K4me3, NF-κB ChIP, nitric oxide assay |
Frontiers in immunology |
Medium |
34276666
|
| 2022 |
RUVBL1 promotes enzalutamide resistance by accumulating in the cytoplasm, where it enhances recruitment of CRAF to PLXNA1 and activates downstream MAPK signaling as an AR-independent survival pathway. |
Co-immunoprecipitation (RUVBL1-CRAF-PLXNA1), siRNA/inhibitor experiments, xenograft models |
Oncogene |
Medium |
35508542
|
| 2022 |
Yeast Rvb1/Rvb2 couple transcription and mRNA fate: they enrich at promoters and mRNAs of alternative glucose metabolism genes during starvation. Engineered Rvb tethering to mRNAs is sufficient to sequester mRNAs into granules, repress translation, and drive further transcriptional upregulation of target genes. |
ChIP-seq, mRNA-seq, RNA immunoprecipitation, engineered tethering system, mRNP granule assay |
eLife |
Medium |
36107469
|
| 2022 |
LINC00839 (lncRNA) recruits RUVBL1 to the TIP60 complex, increases its acetyltransferase activity, and guides the complex to the NRF1 promoter, promoting H4K5 and H4K8 acetylation and NRF1 transcription to activate mitochondrial metabolism. |
Co-immunoprecipitation, ChIP, HAT activity assay, RNA pulldown, siRNA knockdown |
EMBO reports |
Medium |
35876654
|
| 2023 |
GART methylates RUVBL1 at lysine K7, enhancing RUVBL1 stability and thereby aberrantly activating the Wnt/β-catenin signaling pathway to induce tumor stemness; GART methyltransferase activity is centered on the E948 site. |
In vitro methylation assay, site-directed mutagenesis (GART E948, RUVBL1 K7), co-immunoprecipitation, β-catenin reporter assay |
Advanced science |
Medium |
37439412
|
| 2023 |
RUVBL1 controls MYC chromatin binding and modulates MYC-driven EEF1A1 expression, thereby regulating protein synthesis in Ewing sarcoma cells. A high-density CRISPR gene body scan identified the critical MYC-interacting residue in RUVBL1. |
CRISPR screens, ChIP-seq (MYC), ribosome profiling, CRISPR gene body scan, siRNA knockdown |
Advanced science |
Medium |
37075745
|
| 2024 |
DTL (CDT2/DCAF2) ubiquitinates RUVBL1, facilitating its binding to RUVBL2 and β-catenin while attenuating its binding to TIP60. Ubiquitinated RUVBL1 promotes transcriptional regulation of NHEJ repair pathway genes and attenuates TIP60-mediated H4K16 acetylation and homologous recombination repair, thereby enhancing radioresistance. |
Co-immunoprecipitation, ubiquitination assay, HAT assay (H4K16Ac), reporter gene assay, siRNA/overexpression |
Cell death & disease |
Medium |
38609375
|
| 2024 |
RUVBL1/2 interact with YTHDF1 at 40S translation initiation complexes; YTHDF1 binds m6A-modified RUVBL1/2 mRNA to promote their translation. RUVBL1/2 depletion stalls YTHDF1-driven oncogenic translation and impairs MAPK, RAS, and PI3K-AKT signaling in colorectal cancer. |
Co-immunoprecipitation, mass spectrometry, ribosome sequencing, CRISPR screening, m6A analysis |
Cancer research |
Medium |
38900944
|
| 2024 |
RUVBL1 is required for MYC-driven oncogenic and immunoevasive gene expression in pancreatic cancer. Auxin-degron degradation of RUVBL1 leads to complete tumor regression in mice, preceded by immune cell infiltration, establishing RUVBL1 as a nuclear effector of MYC transcriptional programs. |
Auxin-degron system for rapid protein degradation, shRNA library screens in vitro and in vivo, RNA-seq, xenograft models |
Gut |
High |
38821858
|