ArticleMolecular and cellular biology2013
Canonical and kinase activity-independent mechanisms for extracellular signal-regulated kinase 5 (ERK5) nuclear translocation require dissociation of Hsp90 from the ERK5-Cdc37 complex.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 citations in OpenAlex.
- Development of a chaperone-mediated protein degrader targeting ERK5 that efficaciously reduces tumor growth.Cell communication and signaling : CCS · 2026Article
- Bone and Extracellular Signal-Related Kinase 5 (ERK5).Biomolecules · 2024Review
- MAP kinase ERK5 modulates cancer cell sensitivity to extrinsic apoptosis induced by death-receptor agonists.Cell death & disease · 2023Article
- Review
- Article
- Potential of resveratrol in the treatment of interstitial lung disease.Frontiers in pharmacology · 2023Review
- Review
- HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress.Cellular and molecular life sciences : CMLS · 2022Article
- The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival.Cellular and molecular life sciences : CMLS · 2022Article
- A mitochondrial contribution to anti-inflammatory shear stress signaling in vascular endothelial cells.The Journal of cell biology · 2022Article
- Hsp90 and phosphorylation of the Slt2(Mpk1) MAP kinase activation loop are essential for catalytic, but not non-catalytic, Slt2-mediated transcription in yeast.Cell stress & chaperones · 2022Article
- Review
- RSK1 and RSK2 serine/threonine kinases regulate different transcription programs in cancer.Frontiers in cell and developmental biology · 2022Article
- The Potential of Hsp90 in Targeting Pathological Pathways in Cardiac Diseases.Journal of personalized medicine · 2021Review
- The MEK5/ERK5 Pathway in Health and Disease.International journal of molecular sciences · 2021Review
- The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells.Autophagy · 2021Article
- ERK5 Inhibition Induces Autophagy-Mediated Cancer Cell Death by Activating ER Stress.Frontiers in cell and developmental biology · 2021Article
- Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish for….Biochemical Society transactions · 2020Review
- HSP90 Inhibition and Modulation of the Proteome: Therapeutical Implications for Idiopathic Pulmonary Fibrosis (IPF).International journal of molecular sciences · 2020Review
- Discovery of a selective inhibitor of doublecortin like kinase 1.Nature chemical biology · 2020Article
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 mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase 5 (ERK5) plays a crucial role in cell proliferation, regulating gene transcription. ERK5 has a unique C-terminal tail which contains a transcriptional activation domain, and activates transcription by phosphorylating transcription factors and acting itself as a transcriptional coactivator. However, the molecular mechanisms that regulate its nucleocytoplasmatic traffic are unknown. We have used tandem affinity purification to identify proteins that interact with ERK5. We show that ERK5 interacts with the Hsp90-Cdc37 chaperone in resting cells, and that inhibition of Hsp90 or Cdc37 results in ERK5 ubiquitylation and proteasomal degradation. Interestingly, activation of cellular ERK5 induces Hsp90 dissociation from the ERK5-Cdc37 complex, leading to ERK5 nuclear translocation and activation of transcription, by a mechanism which requires the autophosphorylation at its C-terminal tail. Consequently, active ERK5 is no longer sensitive to Hsp90 or Cdc37 inhibitors. Cdc37 overexpression also induces Hsp90 dissociation and the nuclear translocation of a kinase-inactive form of ERK5 which retains transcriptional activity. This is the first example showing that ERK5 transcriptional activity does not require kinase activity. Since Cdc37 cooperates with ERK5 to promote cell proliferation, Cdc37 overexpression (as happens in some cancers) might represent a new, noncanonical mechanism by which ERK5 regulates tumor proliferation.
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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.