ArticleProceedings of the National Academy of Sciences of the United States of America2014
Phosphoproteomic analysis identifies the tumor suppressor PDCD4 as a RSK substrate negatively regulated by 14-3-3.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 84 citations in OpenAlex.
- NRXN3 regulates pyroptosis in intrahepatic cholangiocarcinoma via mediating the phospho-dependent ubiquitination and degradation of caspase-3.Journal of advanced research · 2026Article
- Functional characterisation of tumour suppressor PDCD4 reveals previously undisclosed role in the control of cell adhesion.Nucleic acids research · 2026Article
- Integrative phosphoproteomics reveals kinase-mediated regulation of OCIAD1 and its roles in mitochondrial quality control.Frontiers in bioinformatics · 2026Article
- Targeting Tau Protein with Proximity Inducing Modulators: A New Frontier to Combat Tauopathies.ACS pharmacology & translational science · 2025Review
- Mitochondrial signatures shape phenotype switching and apoptosis in response to PLK1 inhibitors.Life science alliance · 2025Article
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- The Role of p90 Ribosomal S6 Kinase (RSK) in Tyrosine Kinase Inhibitor (TKI)-Induced Cardiotoxicity.Journal of cardiovascular translational research · 2024Review
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- Therapeutic targeting of p90 ribosomal S6 kinase.Frontiers in cell and developmental biology · 2023Review
- B-cell receptor signaling induces proteasomal degradation of PDCD4 via MEK1/2 and mTORC1 in malignant B cells.Cellular signalling · 2022Article
- A non-catalytic herpesviral protein reconfigures ERK-RSK signaling by targeting kinase docking systems in the host.Nature communications · 2022Article
- Metabolism heterogeneity in melanoma fuels deactivation of immunotherapy: Predict before protect.Frontiers in oncology · 2022Review
- Modulation of Phosphoprotein Activity by Phosphorylation Targeting Chimeras (PhosTACs).ACS chemical biology · 2021Article
- p38 regulates the tumor suppressor PDCD4 via the TSC-mTORC1 pathway.Cell stress · 2021Article
- RSK Isoforms in Acute Myeloid Leukemia.Biomedicines · 2021Review
- Clinical Significance of PDCD4 in Melanoma by Subcellular Expression and in Tumor-Associated Immune Cells.Cancers · 2021Article
- PDCD4 limits prooncogenic neuregulin-ErbB signaling.Cellular and molecular life sciences : CMLS · 2021Article
- Eukaryotic translation initiation factors as promising targets in cancer therapy.Cell communication and signaling : CCS · 2020Review
- ERK signalling: a master regulator of cell behaviour, life and fate.Nature reviews. Molecular cell biology · 2020Review
- Systematic Discovery of Short Linear Motifs Decodes Calcineurin Phosphatase Signaling.Molecular cell · 2020Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The Ras/MAPK signaling cascade regulates various biological functions, including cell growth and proliferation. As such, this pathway is frequently deregulated in several types of cancer, including most cases of melanoma. RSK (p90 ribosomal S6 kinase) is a MAPK-activated protein kinase required for melanoma growth and proliferation, but relatively little is known about its exact function and the nature of its substrates. Herein, we used a quantitative phosphoproteomics approach to define the signaling networks regulated by RSK in melanoma. To more accurately predict direct phosphorylation substrates, we defined the RSK consensus phosphorylation motif and found significant overlap with the binding consensus of 14-3-3 proteins. We thus characterized the phospho-dependent 14-3-3 interactome in melanoma cells and found that a large proportion of 14-3-3 binding proteins are also potential RSK substrates. Our results show that RSK phosphorylates the tumor suppressor PDCD4 (programmed cell death protein 4) on two serine residues (Ser76 and Ser457) that regulate its subcellular localization and interaction with 14-3-3 proteins. We found that 14-3-3 binding promotes PDCD4 degradation, suggesting an important role for RSK in the inactivation of PDCD4 in melanoma. In addition to this tumor suppressor, our results suggest the involvement of RSK in a vast array of unexplored biological functions with relevance in oncogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.