ArticleMolecular and cellular biology2015
Vaccinia-Related Kinase 2 Controls the Stability of the Eukaryotic Chaperonin TRiC/CCT by Inhibiting the Deubiquitinating Enzyme USP25.
Article in Molecular and cellular biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 37 citations in OpenAlex.
- Ubiquitin-specific protease 25: a new regulator for cardiovascular and cerebrovascular diseases.Frontiers in cell and developmental biology · 2026Review
- RNF144A-VRK2-G3BP1 axis regulates stress granule assembly.Cell death discovery · 2025Article
- Revisiting the chaperonin T-complex protein-1 ring complex in human health and disease: A proteostasis modulator and beyond.Clinical and translational medicine · 2024Review
- ERK3 Increases Snail Protein Stability by Inhibiting FBXO11-Mediated Snail Ubiquitination.Cancers · 2023Article
- Vaccinia-related kinase 2 variants differentially affect breast cancer growth by regulating kinase activity.Oncology research · 2023Article
- The TRiCky Business of Protein Folding in Health and Disease.Frontiers in cell and developmental biology · 2022Review
- Vaccinia-related kinase 2 drives pancreatic cancer progression by protecting Plk1 from Chfr-mediated degradation.Oncogene · 2021Article
- Vaccinia-related kinase 2 blunts sorafenib's efficacy against hepatocellular carcinoma by disturbing the apoptosis-autophagy balance.Oncogene · 2021Article
- Emerging Roles of Ubiquitin-Specific Protease 25 in Diseases.Frontiers in cell and developmental biology · 2021Review
- Post-Translational Modifications of Deubiquitinating Enzymes: Expanding the Ubiquitin Code.Frontiers in pharmacology · 2021Review
- Proteostasis and Proteotoxicity in the Network Medicine Era.International journal of molecular sciences · 2020Review
- The Vaccinia Virus (VACV) B1 and Cellular VRK2 Kinases Promote VACV Replication Factory Formation through Phosphorylation-Dependent Inhibition of VACV B12.Journal of virology · 2019Article
- The proteostasis network provides targets for neurodegeneration.British journal of pharmacology · 2019Review
- Review
- A quaternary tetramer assembly inhibits the deubiquitinating activity of USP25.Nature communications · 2018Article
- VRK2A is an A-type lamin-dependent nuclear envelope kinase that phosphorylates BAF.Molecular biology of the cell · 2017Article
- Glycogen synthase kinase 3β suppresses polyglutamine aggregation by inhibiting Vaccinia-related kinase 2 activity.Scientific reports · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular chaperones monitor the proper folding of misfolded proteins and function as the first line of defense against mutant protein aggregation in neurodegenerative diseases. The eukaryotic chaperonin TRiC is a potent suppressor of mutant protein aggregation and toxicity in early stages of disease progression. Elucidation of TRiC functional regulation will enable us to better understand the pathological mechanisms of neurodegeneration. We have previously shown that vaccinia-related kinase 2 (VRK2) downregulates TRiC protein levels through the ubiquitin-proteasome system by recruiting the E3 ligase COP1. However, although VRK2 activity was necessary in TRiC downregulation, the phosphorylated substrate was not determined. Here, we report that USP25 is a novel TRiC interacting protein that is also phosphorylated by VRK2. USP25 catalyzed deubiquitination of the TRiC protein and stabilized the chaperonin, thereby reducing accumulation of misfolded polyglutamine protein aggregates. Notably, USP25 deubiquitinating activity was suppressed when VRK2 phosphorylated the Thr(680), Thr(727), and Ser(745) residues. Impaired USP25 deubiquitinating activity after VRK2-mediated phosphorylation may be a critical pathway in TRiC protein destabilization.
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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.