ArticleOncogene2021
Vaccinia-related kinase 2 drives pancreatic cancer progression by protecting Plk1 from Chfr-mediated degradation.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 20 citations in OpenAlex.
- VRK3 promotes KSHV infection by suppressing the antiviral type I interferon response.PLoS pathogens · 2026Article
- Vaccinia-related kinase 2 inhibition elicits vulnerability of glutathione metabolism in pancreatic cancer.Cell death & disease · 2026Article
- VRK2 targeting potentiates anti-PD-1 immunotherapy in hepatocellular carcinoma through MYC destabilization.Nature communications · 2025Article
- EPSD 2.0: An Updated Database of Protein Phosphorylation Sites Across Eukaryotic Species.Genomics, proteomics & bioinformatics · 2025Article
- MLN0905 effectively kills gemcitabine-resistant pancreatic cancer cells by targeting PLK1.European journal of medical research · 2025Article
- The neuroimmune nexus: unraveling the role of the mtDNA-cGAS-STING signal pathway in Alzheimer's disease.Molecular neurodegeneration · 2025Review
- Elevated FBXL6 expression in hepatocytes activates VRK2-transketolase-ROS-mTOR-mediated immune evasion and liver cancer metastasis in mice.Experimental & molecular medicine · 2023Article
- Mitochondrial DNA-targeted therapy: A novel approach to combat cancer.Cell insight · 2023Review
- Maintaining Genome Integrity: Protein Kinases and Phosphatases Orchestrate the Balancing Act of DNA Double-Strand Breaks Repair in Cancer.International journal of molecular sciences · 2023Review
- Ubiquitin signaling in pancreatic ductal adenocarcinoma.Frontiers in molecular biosciences · 2023Review
- Identification of CFHR4 as a Potential Prognosis Biomarker Associated With lmmune Infiltrates in Hepatocellular Carcinoma.Frontiers in immunology · 2022Article
- VRK2 activates TNFα/NF-κB signaling by phosphorylating IKKβ in pancreatic cancer.International journal of biological sciences · 2022Article
- A Novel Gene Signature Associated With "E2F Target" Pathway for Predicting the Prognosis of Prostate Cancer.Frontiers in molecular biosciences · 2022Article
- Polo-like kinase 1 is related with malignant characteristics and inhibits macrophages infiltration in glioma.Frontiers in immunology · 2022Article
- Combination Approaches to Target PD-1 Signaling in Cancer.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As a key cell cycle regulator, polo-like kinase 1 (Plk1) has been recognized as a crucial factor involved in the progression of pancreatic cancer (PC). However, its regulatory mechanism is poorly understood. Here, we present evidence that Plk1 is a novel substrate of vaccinia-related kinase 2 (VRK2), a serine-threonine kinase that is highly expressed and predicts poor prognosis in PC. VRK2 phosphorylates Plk1 at threonine 210 and protects it from ubiquitin-dependent proteasomal degradation. We showed that mechanistically complement factor H-related protein (CFHR), as a major E3 ligase, promotes Plk1 degradation by ubiquitinating it at lysine 209. Phosphorylation of Plk1 at threonine 210 by VRK2 interferes with the interaction of Chfr with Plk1 and antagonizes Plk1 ubiquitination, thereby stabilizing the Plk1 protein. Taken together, our data reveal a mechanism of Plk1 overexpression in PC and provide evidence for targeting VRK2 as a potential therapeutic strategy.
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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.