ArticleMolecular and cellular biology2014
Vaccinia-related kinase 2 mediates accumulation of polyglutamine aggregates via negative regulation of the chaperonin TRiC.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Revisiting the chaperonin T-complex protein-1 ring complex in human health and disease: A proteostasis modulator and beyond.Clinical and translational medicine · 2024Review
- 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
- Post-Translational Modifications of Deubiquitinating Enzymes: Expanding the Ubiquitin Code.Frontiers in pharmacology · 2021Review
- The Molecular Chaperone CCT/TRiC: An Essential Component of Proteostasis and a Potential Modulator of Protein Aggregation.Frontiers in genetics · 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
- Article
- Murine cytomegalovirus M72 promotes acute virus replication in vivo and is a substrate of the TRiC/CCT complex.Virology · 2018Article
- Selective uptake of epidermal growth factor-conjugated gold nanoparticle (EGF-GNP) facilitates non-thermal plasma (NTP)-mediated cell death.Scientific reports · 2017Article
- 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
- Vaccinia-Related Kinase 2 Controls the Stability of the Eukaryotic Chaperonin TRiC/CCT by Inhibiting the Deubiquitinating Enzyme USP25.Molecular and cellular biology · 2015Article
- A direct regulatory interaction between chaperonin TRiC and stress-responsive transcription factor HSF1.Cell reports · 2014Article
- Therapeutic Approaches for Inhibition of Protein Aggregation in Huntington's Disease.Experimental neurobiology · 2014Review
- Luteolin suppresses cancer cell proliferation by targeting vaccinia-related kinase 1.PloS one · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Misfolding of proteins containing abnormal expansions of polyglutamine (polyQ) repeats is associated with cytotoxicity in several neurodegenerative disorders, including Huntington's disease. Recently, the eukaryotic chaperonin TRiC hetero-oligomeric complex has been shown to play an important role in protecting cells against the accumulation of misfolded polyQ protein aggregates. It is essential to elucidate how TRiC function is regulated to better understand the pathological mechanism of polyQ aggregation. Here, we propose that vaccinia-related kinase 2 (VRK2) is a critical enzyme that negatively regulates TRiC. In mammalian cells, overexpression of wild-type VRK2 decreased endogenous TRiC protein levels by promoting TRiC ubiquitination, but a VRK2 kinase-dead mutant did not. Interestingly, VRK2-mediated downregulation of TRiC increased aggregate formation of a polyQ-expanded huntingtin fragment. This effect was ameliorated by rescue of TRiC protein levels. Notably, small interference RNA-mediated knockdown of VRK2 enhanced TRiC protein stability and decreased polyQ aggregation. The VRK2-mediated reduction of TRiC protein levels was subsequent to the recruitment of COP1 E3 ligase. Among the members of the COP1 E3 ligase complex, VRK2 interacted with RBX1 and increased E3 ligase activity on TRiC in vitro. Taken together, these results demonstrate that VRK2 is crucial to regulate the ubiquitination-proteosomal degradation of TRiC, which controls folding of polyglutamine proteins involved in Huntington's disease.
Indexed as
Identifiers
What OpenQuestion holds
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.