| 2010 |
RioK1 is a stoichiometric component of the PRMT5 complex, binding PRMT5 in a mutually exclusive fashion with pICln. RioK1 and pICln both bind to a PRMT5-WD45/MEP50 core, forming distinct complexes. RioK1 acts as an adapter protein that recruits the RNA-binding protein nucleolin to the PRMT5 complex for its symmetrical arginine dimethylation. |
Biochemical purification, co-immunoprecipitation, stoichiometric complex analysis, in vitro methylation assay |
The Journal of biological chemistry |
High |
21081503
|
| 2016 |
RIOK1 is a co-complex protein of PRMT5 and its depletion creates a vulnerability in MTAP-deleted cancer cells, placing RIOK1 functionally downstream of MTA accumulation-mediated PRMT5 inhibition in the MAT2A/PRMT5/RIOK1 axis. |
shRNA screening, metabolomic profiling, biochemical methyltransferase inhibition assays |
Cell reports |
Medium |
27068473
|
| 2018 |
RIOK1 is methylated at K411 by SETD7 methyltransferase; LSD1 reverses this methylation. The K411-methylated form is recognized by FBXO6 (via its FBA domain), leading to RIOK1 ubiquitination and degradation. CK2 phosphorylates RIOK1 at T410, which stabilizes RIOK1 by antagonizing K411 methylation and blocking FBXO6 recruitment. This methylation-phosphorylation switch regulates RIOK1 protein stability and tumor growth/metastasis. |
In vitro methylation/phosphorylation assays, mutagenesis (K411R), co-immunoprecipitation, ubiquitination assays, mouse xenograft models |
eLife |
High |
29384474
|
| 2018 |
RIOK1 kinase activity is required for cancer cell survival irrespective of MTAP status. Using CRISPR/Cas9-generated analog-sensitive alleles, differential kinase activity requirement was NOT detected between MTAP-proficient and MTAP-deleted cells, contrasting with the differential PRMT5 dependency. |
CRISPR/Cas9 analog-sensitive kinase allele engineering, isogenic cell line comparison, chemical-genetic inhibition |
Oncotarget |
Medium |
29983885
|
| 2017 |
RIOK1 knockdown in RAS-mutant cancer cells impairs proliferation and invasiveness, activates NF-κB signaling, and reduces expression of pro-invasive proteins Metadherin and Stathmin1. RIOK1 promotes cell cycle progression. These effects are specific to RAS-mutant cells and not observed in RAS-wildtype cells. |
shRNA knockdown, 3D culture, proteomics, NF-κB reporter assays, in vivo lung colonization assay |
EBioMedicine |
Medium |
28499923
|
| 2021 |
The binding interface between RioK1 and the PRMT5 TIM barrel domain was mapped by peptide truncation and mutation studies. A consensus amino acid sequence GQF[D/E]DA[E/D] is involved in binding. Protein crystallography revealed that the RioK1-derived peptide interacts with a novel protein-protein interaction site on PRMT5, distinct from the pICln binding site. |
Peptide truncation and mutation studies, protein crystallography |
Chembiochem : a European journal of chemical biology |
High |
33624332
|
| 2022 |
RIOK1 phosphorylates G3BP2 at Thr226, increasing G3BP2 activity. RIOK1-mediated G3BP2 phosphorylation facilitates MDM2-mediated ubiquitination of p53, suppressing the p53 signaling pathway and contributing to radioresistance in colorectal cancer. RIOK1 and G3BP2 physically interact. |
Co-immunoprecipitation, in vitro kinase assay (phosphorylation at Thr226), ubiquitination assay, knockdown/inhibitor experiments in vitro and in vivo |
Oncogene |
Medium |
35589951
|
| 2022 |
NF90 (Nuclear Factor 90) specifically interacts with the PRMT5-WD45-RioK1 complex and is symmetrically dimethylated by PRMT5 within the RG-rich region of its C-terminus, establishing NF90 as a new substrate recruited via the RioK1 adaptor. |
Co-immunoprecipitation, in vitro/in vivo methylation assay, PRMT5 inhibitor treatment |
Biological chemistry |
Medium |
36040368
|
| 2018 |
In C. elegans, riok-1 acts upstream of the p38 MAPK/pmk-1 pathway as a negative regulator (suppressor) of innate immune signaling. Genetic epistasis placed riok-1 downstream of skn-1 (a p38 MAPK transcription factor), suggesting a negative feedback loop: SKN-1 → RIOK-1 ⊣ p38 MAPK/PMK-1. |
RNAi knockdown, genetic epistasis analysis, quantitative RT-PCR, infection resistance assays |
Frontiers in immunology |
Medium |
29719537
|
| 2014 |
In C. elegans, depletion of riok-1 (ortholog of mammalian RIOK1) suppresses the multi-vulva phenotype caused by oncogenic Ras/Raf signaling, placing riok-1 as a modulator of the Ras signaling pathway. |
RNAi screen in C. elegans, multi-vulva phenotype assay, promoter-GFP expression analysis |
Gene expression patterns : GEP |
Medium |
24929033
|
| 2024 |
RIOK1 forms a trimeric complex with SPC25 and MYH9, where SPC25 acts as a scaffold. Within this complex, RIOK1 phosphorylates MYH9 at Ser1943. This phosphorylation causes MYH9 to disengage from the cytoskeleton and accumulate in the nucleus, potentiating CTNNB1 transcription and Wnt/β-catenin signaling activation, promoting cancer stem cell phenotypes and platinum resistance. |
Co-immunoprecipitation, in vitro kinase assay (phosphorylation at Ser1943), mutagenesis, nuclear fractionation, competitive inhibitory peptide (CBP1), patient-derived organoids |
Advanced science (Weinheim, Baden-Wurttemberg, Germany) |
High |
39488790
|
| 2025 |
RIOK1 undergoes liquid-liquid phase separation and incorporates IGF2BP1 and G3BP1 into stress granules. These RIOK1-positive stress granules sequester PTEN mRNA, reducing its translation, thereby activating the pentose phosphate pathway and facilitating stress resolution and cytoprotection against tyrosine kinase inhibitors in hepatocellular carcinoma. |
Phase separation assays, stress granule immunofluorescence, mRNA translation assays, RNA immunoprecipitation, metabolic profiling, in vitro and in vivo TKI resistance models |
Nature cancer |
Medium |
40467995
|
| 2025 |
RIOK1 interacts with YBX1 and induces phosphorylation of YBX1 at Ser165, promoting nuclear localization of YBX1, which in turn activates the JAK2/STAT3 pathway and increases lenvatinib resistance in hepatocellular carcinoma cells. |
Co-immunoprecipitation, phosphorylation site identification, nuclear fractionation, knockdown/overexpression functional assays, mouse xenograft |
Biochimica et biophysica acta. Molecular cell research |
Medium |
41354180
|
| 2023 |
RIOK1 is identified as a downstream target gene of the c-myc/E2F transcription factors in prostate cancer. A dominant-negative RIOK1-D324A mutant reduces PCa cell proliferation, and toyocamycin treatment (RIOK1 biochemical inhibitor) causes rapid decreases in RIOK1 protein, total rRNA content, and shifts the 28S/18S rRNA ratio, consistent with a role in ribosome biogenesis. |
Chromatin immunoprecipitation/transcription factor target analysis, dominant-negative mutagenesis (D324A), rRNA quantification, pharmacological inhibition with toyocamycin |
The American journal of pathology |
Medium |
37301535
|