ArticleCell death & disease2013
The p90 ribosomal S6 kinase (RSK) inhibitor BI-D1870 prevents gamma irradiation-induced apoptosis and mediates senescence via RSK- and p53-independent accumulation of p21WAF1/CIP1.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 38 citations in OpenAlex.
- Biological effects of orotic acid on ovine mammary epithelial cells and associated regulatory pathways study by transcriptomics.BMC veterinary research · 2026Article
- High-mobility network hydrogel microsphere system to combat chondrocyte senescence for enhanced cartilage repair and regeneration.Materials today. Bio · 2025Article
- MLN0905, a new inhibitor of Polo-like kinase 1 (PLK1), enhances the efficiency of lenalidomide in promoting the apoptosis of multiple myeloma cell lines.Investigational new drugs · 2025Article
- Mitochondrial signatures shape phenotype switching and apoptosis in response to PLK1 inhibitors.Life science alliance · 2025Article
- Mitomycin C and its analog trigger cytotoxicity in MCF-7 and K562 cancer cells through the regulation of RAS and MAPK/ERK pathways.Chemico-biological interactions · 2024Article
- Inhibition of p90RSK Ameliorates PDGF-BB-Mediated Phenotypic Change of Vascular Smooth Muscle Cell and Subsequent Hyperplasia of Neointima.International journal of molecular sciences · 2023Article
- Role of p53 in Regulating Radiation Responses.Life (Basel, Switzerland) · 2022Review
- Identifying requirements for RSK2 specific inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Inhibition of AKT signalling by benzoxazine derivative LTUR6 through the modulation of downstream kinases.Investigational new drugs · 2019Article
- Covalent Inhibition in Drug Discovery.ChemMedChem · 2019Review
- Alterations in Phosphorylation of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection.Cell reports · 2019Article
- Gossypin inhibits gastric cancer growth by direct targeting of AURKA and RSK2.Phytotherapy research : PTR · 2019Article
- Coxsackieviruses B3 infection of myocardial microvascular endothelial cells activates fractalkine via the ERK1/2 signaling pathway.Molecular medicine reports · 2017Article
- p90RSK Blockade Inhibits Dual BRAF and MEK Inhibitor-Resistant Melanoma by Targeting Protein Synthesis.The Journal of investigative dermatology · 2017Article
- The DEAD-box RNA helicase DDX41 is a novel repressor of p21The Journal of biological chemistry · 2017Article
- RSK1 protects P-glycoprotein/ABCB1 against ubiquitin-proteasomal degradation by downregulating the ubiquitin-conjugating enzyme E2 R1.Scientific reports · 2016Article
- Elevated ERK/p90 ribosomal S6 kinase activity underlies audiogenic seizure susceptibility in fragile X mice.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- miR-30e controls DNA damage-induced stress responses by modulating expression of the CDK inhibitor p21WAF1/CIP1 and caspase-3.Oncotarget · 2016Article
- Ras-activated RSK1 phosphorylates EBP50 to regulate its nuclear localization and promote cell proliferation.Oncotarget · 2016Article
- NaCl pretreatment attenuates H.pylori-induced DNA damage and exacerbates proliferation of gastric epithelial cells (GES-1).Infectious agents and cancer · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p90 ribosomal S6 kinase (RSK) family is a group of highly conserved Ser/Thr kinases that promote cell proliferation, growth, motility and survival. As they are almost exclusively activated downstream of extracellular signal-regulated kinases 1 and 2 (ERK1/2), therapeutic intervention by RSK inhibition is less likely to produce such severe side effects as those observed following inhibition of the upstream master regulators Raf, MEK and ERK1/2. Here, we report that BI-D1870, a potent small molecule inhibitor of RSKs, induces apoptosis, although preferentially, in a p21-deficient background. On the other hand, BI-D1870 also induces a strong transcription- and p53-independent accumulation of p21 protein and protects cells from gamma irradiation (γIR)-induced apoptosis, driving them into senescence even in the absence of γIR. Although we identified p21 in in vitro kinase assays as a novel RSK substrate that specifically becomes phosphorylated by RSK1-3 at Ser116 and Ser146, RNA-interference, overexpression and co-immunoprecipitation studies as well as the use of SL0101, another specific RSK inhibitor, revealed that BI-D1870 mediates p21 accumulation via a yet unknown pathway that, besides its off-site targets polo-like kinase-1 and AuroraB, also does also not involve RSKs. Thus, this novel off-target effect of BI-D1870 should be taken into serious consideration in future studies investigating the role of RSKs in cellular signaling and tumorigenesis.
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