ArticlePLoS biology2021
MARK2 phosphorylates eIF2α in response to proteotoxic stress.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 36 citations in OpenAlex.
- Global cellular responses to lysosomal damage.Current biology : CB · 2026Review
- The unfolded protein response and its activation by insulin in muscle are not altered by obesity or type 2 diabetes.Clinical science (London, England : 1979) · 2026Article
- Review
- Inhibiting translation elongation by reducing eIF5A activity induces feedback inhibition of initiation, limiting tumour cell proliferation.Nature communications · 2025Article
- MARK2 regulates C9orf72 repeat-associated non-AUG translation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Granular Insights on Innate and Intrinsic Immunity to Flaviviruses.Microorganisms · 2025Review
- Integrated stress response in Behçet disease: expression analyses in peripheral blood and synovial monocytes.Rheumatology international · 2025Article
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- The SHFV nsp2 and nucleocapsid proteins recruit G3BP1 to sites of viral replication, but stress granules are not induced by the infection.Journal of virology · 2025Article
- RNA dysregulation in neurodegenerative diseases.The EMBO journal · 2025Review
- Calcium signaling from damaged lysosomes induces cytoprotective stress granules.The EMBO journal · 2024Article
- A mechanism that transduces lysosomal damage signals to stress granule formation for cell survival.bioRxiv : the preprint server for biology · 2024Article
- ATF4 Signaling in HIV-1 Infection: Viral Subversion of a Stress Response Transcription Factor.Biology · 2024Review
- Is there a localized role for translational quality control?RNA (New York, N.Y.) · 2023Article
- Article
- Molecular Chaperones' Potential against Defective Proteostasis of Amyotrophic Lateral Sclerosis.Cells · 2023Review
- Review
- Signaling plasticity in the integrated stress response.Frontiers in cell and developmental biology · 2023Review
- Induction of ATF4-Regulated Atrogenes Is Uncoupled from Muscle Atrophy during Disuse in Halofuginone-Treated Mice and in Hibernating Brown Bears.International journal of molecular sciences · 2022Article
- Regulation and function of elF2B in neurological and metabolic disorders.Bioscience reports · 2022Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The regulation of protein synthesis is essential for maintaining cellular homeostasis, especially during stress responses, and its dysregulation could underlie the development of human diseases. The critical step during translation regulation is the phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α). Here we report the identification of a direct kinase of eIF2α, microtubule affinity-regulating kinase 2 (MARK2), which phosphorylates eIF2α in response to proteotoxic stress. The activity of MARK2 was confirmed in the cells lacking the 4 previously known eIF2α kinases. MARK2 itself was found to be a substrate of protein kinase C delta (PKCδ), which serves as a sensor for protein misfolding stress through a dynamic interaction with heat shock protein 90 (HSP90). Both MARK2 and PKCδ are activated via phosphorylation in proteotoxicity-associated neurodegenerative mouse models and in human patients with amyotrophic lateral sclerosis (ALS). These results reveal a PKCδ-MARK2-eIF2α cascade that may play a critical role in cellular proteotoxic stress responses and human diseases.
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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.