ArticleMolecular and cellular biology2006
p53 downregulates its activating vaccinia-related kinase 1, forming a new autoregulatory loop.
Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 64 citations in OpenAlex.
- Nuclear functions regulated by the VRK1 kinase.Nucleus (Austin, Tex.) · 2024Review
- Dysfunctional Homozygous VRK1-D263G Variant Impairs the Assembly of Cajal Bodies and DNA Damage Response in Hereditary Spastic Paraplegia.Neurology. Genetics · 2021Article
- Adult-Onset Spinal Muscular Atrophy due to Mutations in theNeurology. Genetics · 2021Article
- Identification of VRK1 as a New Neuroblastoma Tumor Progression Marker Regulating Cell Proliferation.Cancers · 2020Article
- VRK1 Phosphorylates Tip60/KAT5 and Is Required for H4K16 Acetylation in Response to DNA Damage.Cancers · 2020Article
- Downregulation of VRK1 reduces the expression of BANF1 and suppresses the proliferative and migratory activity of esophageal cancer cells.Oncology letters · 2020Article
- VRK1 functional insufficiency due to alterations in protein stability or kinase activity of human VRK1 pathogenic variants implicated in neuromotor syndromes.Scientific reports · 2019Article
- Olaparib and ionizing radiation trigger a cooperative DNA-damage repair response that is impaired by depletion of the VRK1 chromatin kinase.Journal of experimental & clinical cancer research : CR · 2019Article
- Implication of the VRK1 chromatin kinase in the signaling responses to DNA damage: a therapeutic target?Cellular and molecular life sciences : CMLS · 2018Review
- Oncogenic Sox2 regulates and cooperates with VRK1 in cell cycle progression and differentiation.Scientific reports · 2016Article
- Expanding Phenotype of VRK1 Mutations in Motor Neuron Disease.Journal of clinical neuromuscular disease · 2015Article
- Vaccinia-related kinase 1 promotes hepatocellular carcinoma by controlling the levels of cell cycle regulators associated with G1/S transition.Oncotarget · 2015Article
- Ursolic acid exerts anti-cancer activity by suppressing vaccinia-related kinase 1-mediated damage repair in lung cancer cells.Scientific reports · 2015Article
- VRK1 regulates Cajal body dynamics and protects coilin from proteasomal degradation in cell cycle.Scientific reports · 2015Article
- The changes of vaccinia related kinase 1 in grafted heart after rat heart transplantation.Journal of thoracic disease · 2014Article
- Article
- Vaccinia-related kinase 1 (VRK1) confers resistance to DNA-damaging agents in human breast cancer by affecting DNA damage response.Oncotarget · 2014Article
- Mutations in VRK1 associated with complex motor and sensory axonal neuropathy plus microcephaly.JAMA neurology · 2013Article
- VRK2 identifies a subgroup of primary high-grade astrocytomas with a better prognosis.BMC clinical pathology · 2013Article
- Sensitivity of the kinase activity of human vaccinia-related kinase proteins to toxic metals.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2013Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The stable accumulation of p53 is detrimental to the cell because it blocks cell growth and division. Therefore, increases in p53 levels are tightly regulated, mainly by its transcriptional target, mdm2, that downregulates p53. Elucidation of new signaling pathways requires the characterization of the members and the nature of their connection. Vaccinia-related kinase 1 (VRK1) contributes to p53 stabilization by partly interfering with its mdm2-mediated degradation, among other mechanisms; therefore, it is likely that some form of autoregulation between VRK1 and p53 must occur. We report here the identification of an autoregulatory loop between p53 and its stabilizing VRK1. There is an inverse correlation between VRK1 and p53 levels in cell lines, and induction of p53 by UV light downregulates VRK1 in fibroblasts. As the amount of p53 protein increases, there is a downregulation of the VRK1 protein level independent of its promoter. This effect is indirect but requires a transcriptionally active p53. The three most common transcriptionally inactive mutations detected in hereditary (Li-Fraumeni syndrome) and sporadic human cancer, p53(R175H), p53(R248W), and p53(R273H), as well as p53(R280K), are unable to induce downregulation of VRK1 protein. The p53 isoforms Delta40p53 and p53beta, lacking the transactivation and oligomerization domains, respectively, do not downregulate VRK1. VRK1 downregulation induced by p53 is independent of mdm2 activity and proteasome-mediated degradation since it occurs in the presence of proteasome inhibitors and in mdm2-deficient cells. The degradation of VRK1 is sensitive to chloroquine, an inhibitor of the late endosome-lysosome transport, and to serine protease inhibitors of the lysosomal pathway.
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