ArticleProceedings of the National Academy of Sciences of the United States of America2016
ERK5 kinase activity is dispensable for cellular immune response and proliferation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 93 citations in OpenAlex.
- AXL is a novel ERK5/KLF4 target in MEK inhibitor-treated melanoma.Neoplasia (New York, N.Y.) · 2026Article
- XMD8-92 and JWG-045 exhibit anti-ferroptotic activities, independently of inhibiting ERK5.Scientific reports · 2026Article
- Development of a chaperone-mediated protein degrader targeting ERK5 that efficaciously reduces tumor growth.Cell communication and signaling : CCS · 2026Article
- The Discovery of Small ERK5 Inhibitors via Structure-Based Virtual Screening, Biological Evaluation and MD Simulations.Molecules (Basel, Switzerland) · 2025Article
- The MEK5/ERK5 pathway promotes the activation of the Hedgehog/GLI signaling in melanoma cells.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Anti-cancer Effects of 1,4-Dialkoxynaphthalene-Imidazolium Salt Derivatives through ERK5 kinase activity inhibition.Scientific reports · 2025Article
- Bone and Extracellular Signal-Related Kinase 5 (ERK5).Biomolecules · 2024Review
- Role of Mitogen-Activated Protein (MAP) Kinase Pathways in Metabolic Diseases.Genome integrity · 2024Review
- MAP kinase ERK5 modulates cancer cell sensitivity to extrinsic apoptosis induced by death-receptor agonists.Cell death & disease · 2023Article
- Aerobic Exercise Alters the Melanoma Microenvironment and Modulates ERK5 S496 Phosphorylation.Cancer immunology research · 2023Article
- Identification of a Novel ERK5 (MAPK7) Inhibitor, MHJ-627, and Verification of Its Potent Anticancer Efficacy in Cervical Cancer HeLa Cells.Current issues in molecular biology · 2023Article
- An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis.Circulation research · 2023Article
- Modulation of ERK5 Activity as a Therapeutic Anti-Cancer Strategy.Journal of medicinal chemistry · 2023Review
- Review
- Article
- The significance of ERK5 catalytic-independent functions in disease pathways.Frontiers in cell and developmental biology · 2023Review
- MEK5-ERK5 Axis Promotes Self-renewal and Tumorigenicity of Glioma Stem Cells.Cancer research communications · 2023Article
- Artificial intelligence to guide precision anticancer therapy with multitargeted kinase inhibitors.BMC cancer · 2022Article
- Acute pharmacological degradation of ERK5 does not inhibit cellular immune response or proliferation.Cell chemical biology · 2022Article
- The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival.Cellular and molecular life sciences : CMLS · 2022Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Unlike other members of the MAPK family, ERK5 contains a large C-terminal domain with transcriptional activation capability in addition to an N-terminal canonical kinase domain. Genetic deletion of ERK5 is embryonic lethal, and tissue-restricted deletions have profound effects on erythroid development, cardiac function, and neurogenesis. In addition, depletion of ERK5 is antiinflammatory and antitumorigenic. Small molecule inhibition of ERK5 has been shown to have promising activity in cell and animal models of inflammation and oncology. Here we report the synthesis and biological characterization of potent, selective ERK5 inhibitors. In contrast to both genetic depletion/deletion of ERK5 and inhibition with previously reported compounds, inhibition of the kinase with the most selective of the new inhibitors had no antiinflammatory or antiproliferative activity. The source of efficacy in previously reported ERK5 inhibitors is shown to be off-target activity on bromodomains, conserved protein modules involved in recognition of acetyl-lysine residues during transcriptional processes. It is likely that phenotypes reported from genetic deletion or depletion of ERK5 arise from removal of a noncatalytic function of ERK5. The newly reported inhibitors should be useful in determining which of the many reported phenotypes are due to kinase activity and delineate which can be pharmacologically targeted.
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Registered trials
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.