ArticlePLoS computational biology2016
Non-degradative Ubiquitination of Protein Kinases.
Article in PLoS computational biology, 2016. 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, 41 citations in OpenAlex.
- MYC-Mediated USP39 Upregulation Stabilizes SRSF1 in Pancreatic Cancer.Molecular cancer research : MCR · 2026Article
- Dapagliflozin Attenuates NKCC2 Protein Expression and Alleviates Diabetic Kidney Disease in Salt Loaded-Hypertensive Diabetic Db/Db Mice.FASEB bioAdvances · 2026Article
- Protein Post-Translational Modifications in UV-Induced Skin Damage.Experimental dermatology · 2026Review
- Ubiquitination-Driven Reprogramming of Proteostasis in Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Metabolic and post-translational modifications in sepsis-associated immune dysfunction: a conceptual framework.Frontiers in immunology · 2026Review
- E3 ubiquitin ligases in neurodegenerative diseases.Military Medical Research · 2026Review
- MARCH2-mediated Lys63-linked polyubiquitination promotes metastasis by modulating the catalytic activity of TGF-β type I receptor.Cell death & disease · 2025Article
- Dual role of proliferating cell nuclear antigen monoubiquitination in facilitating Fanconi anemia-mediated interstrand crosslink repair.PNAS nexus · 2024Article
- Post-ischemic ubiquitination at the postsynaptic density reversibly influences the activity of ischemia-relevant kinases.Communications biology · 2024Article
- Activating transcription factor 3: A potential therapeutic target for inflammatory pulmonary diseases.Immunity, inflammation and disease · 2023Review
- The ubiquitination landscape of the influenza A virus polymerase.Nature communications · 2023Article
- Oncogenic deubiquitination controls tyrosine kinase signaling and therapy response in acute lymphoblastic leukemia.Science advances · 2022Article
- Thirty years of molecular dynamics simulations on posttranslational modifications of proteins.Physical chemistry chemical physics : PCCP · 2022Review
- Deubiquitinating enzymes and the proteasome regulate preferential sets of ubiquitin substrates.Nature communications · 2022Article
- Global post-translational modification profiling of HIV-1-infected cells reveals mechanisms of host cellular pathway remodeling.Cell reports · 2022Article
- Site-specific ubiquitination: Deconstructing the degradation tag.Current opinion in structural biology · 2022Review
- A walk-through MAPK structure and functionality with the 30-year-old yeast MAPK Slt2.International microbiology : the official journal of the Spanish Society for Microbiology · 2021Review
- Ubiquitylation of MLKL at lysine 219 positively regulates necroptosis-induced tissue injury and pathogen clearance.Nature communications · 2021Article
- Ubiquitination and Deubiquitination in Oral Disease.International journal of molecular sciences · 2021Review
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Growing evidence supports other regulatory roles for protein ubiquitination in addition to serving as a tag for proteasomal degradation. In contrast to other common post-translational modifications, such as phosphorylation, little is known about how non-degradative ubiquitination modulates protein structure, dynamics, and function. Due to the wealth of knowledge concerning protein kinase structure and regulation, we examined kinase ubiquitination using ubiquitin remnant immunoaffinity enrichment and quantitative mass spectrometry to identify ubiquitinated kinases and the sites of ubiquitination in Jurkat and HEK293 cells. We find that, unlike phosphorylation, ubiquitination most commonly occurs in structured domains, and on the kinase domain, ubiquitination is concentrated in regions known to be important for regulating activity. We hypothesized that ubiquitination, like other post-translational modifications, may alter the conformational equilibrium of the modified protein. We chose one human kinase, ZAP-70, to simulate using molecular dynamics with and without a monoubiquitin modification. In Jurkat cells, ZAP-70 is ubiquitinated at several sites that are not sensitive to proteasome inhibition and thus may have other regulatory roles. Our simulations show that ubiquitination influences the conformational ensemble of ZAP-70 in a site-dependent manner. When monoubiquitinated at K377, near the C-helix, the active conformation of the ZAP-70 C-helix is disrupted. In contrast, when monoubiquitinated at K476, near the kinase hinge region, an active-like ZAP-70 C-helix conformation is stabilized. These results lead to testable hypotheses that ubiquitination directly modulates kinase activity, and that ubiquitination is likely to alter structure, dynamics, and function in other protein classes as well.
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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.