ArticleMolecular cell2020
Proline Hydroxylation Primes Protein Kinases for Autophosphorylation and Activation.
Article in Molecular cell, 2020. 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, 35 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Hydroxylation of the HIV-1 antisense protein promotes immune evasion of HIV-1 via modulation of TBK1.Nature communications · 2026Article
- Largely Distinct Post-Translational Modifications Differentiate Skeletal Muscle Wasting Caused by Cancer, Dexamethasone and Aging.Journal of cachexia, sarcopenia and muscle · 2026Article
- The dual fate of DYRK2 in cancer: balancing the light and dark side of tumorigenesis.Cancer metastasis reviews · 2026Review
- Critical role of the CMGC insert sequence for tyrosine autophosphorylation in the protein kinase DYRK1B.Scientific reports · 2025Article
- EGLN1 (PHD2) role in tumor microenvironment: insights for therapeutic targeting.Experimental & molecular medicine · 2025Review
- Bacterial effectors mediate kinase reprogramming through mimicry of conserved eukaryotic motifs.EMBO reports · 2025Article
- Melanoma-derived extracellular vesicles transfer proangiogenic factors.Oncology research · 2025Review
- Article
- P4HA2 hydroxylates SUFU to regulate the paracrine Hedgehog signaling and promote B-cell lymphoma progression.Leukemia · 2024Article
- Oxygen enhances antiviral innate immunity through maintenance of EGLN1-catalyzed proline hydroxylation of IRF3.Nature communications · 2024Article
- The P124A mutation of SRP14 alters its migration on SDS-PAGE without impacting its function.Acta biochimica et biophysica Sinica · 2024Article
- Hypoxia-inducible factor in cancer: from pathway regulation to therapeutic opportunity.BMJ oncology · 2024Review
- Oxygen-regulated post-translation modifications as master signalling pathway in cells.EMBO reports · 2023Review
- Regulation of CMGC kinases by hypoxia.BMB reports · 2023Review
- Functions of SRPK, CLK and DYRK kinases in stem cells, development, and human developmental disorders.FEBS letters · 2023Review
- Proline hydroxylation of CREB-regulated transcriptional coactivator 2 controls hepatic glucose metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The multifaceted role of EGLN family prolyl hydroxylases in cancer: going beyond HIF regulation.Oncogene · 2022Review
- Hydroxyproline in animal metabolism, nutrition, and cell signaling.Amino acids · 2022Review
- Differential maturation and chaperone dependence of the paralogous protein kinases DYRK1A and DYRK1B.Scientific reports · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of dual-specificity tyrosine-phosphorylation-regulated kinases 1A and 1B (DYRK1A and DYRK1B) requires prolyl hydroxylation by PHD1 prolyl hydroxylase. Prolyl hydroxylation of DYRK1 initiates a cascade of events leading to the release of molecular constraints on von Hippel-Lindau (VHL) ubiquitin ligase tumor suppressor function. However, the proline residue of DYRK1 targeted by hydroxylation and the role of prolyl hydroxylation in tyrosine autophosphorylation of DYRK1 are unknown. We found that a highly conserved proline in the CMGC insert of the DYRK1 kinase domain is hydroxylated by PHD1, and this event precedes tyrosine autophosphorylation. Mutation of the hydroxylation acceptor proline precludes tyrosine autophosphorylation and folding of DYRK1, resulting in a kinase unable to preserve VHL function and lacking glioma suppression activity. The consensus proline sequence is shared by most CMGC kinases, and prolyl hydroxylation is essential for catalytic activation. Thus, formation of prolyl-hydroxylated intermediates is a novel mechanism of kinase maturation and likely a general mechanism of regulation of CMGC kinases in eukaryotes.
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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.