ArticleThe Journal of biological chemistry2008
A central role for CK1 in catalyzing phosphorylation of the p53 transactivation domain at serine 20 after HHV-6B viral infection.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
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- Integrative analysis reveals therapeutic potential of pyrvinium pamoate in Merkel cell carcinoma.bioRxiv : the preprint server for biology · 2024Article
- The CK1ε/SIAH1 axis regulates AXIN1 stability in colorectal cancer cells.Molecular oncology · 2024Article
- CK1 and PP1 regulate Rift Valley fever virus genome replication through L protein phosphorylation.Antiviral research · 2024Article
- 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
- Targeting Protein Kinases in Blood Cancer: Focusing on CK1α and CK2.International journal of molecular sciences · 2021Review
- SIRT1 modulates cell cycle progression by regulating CHK2 acetylation-phosphorylation.Cell death and differentiation · 2020Article
- IC261, a specific inhibitor of CK1δ/ε, promotes aerobic glycolysis through p53-dependent mechanisms in colon cancer.International journal of biological sciences · 2020Article
- Review
- Article
- Casein kinase 1α: biological mechanisms and theranostic potential.Cell communication and signaling : CCS · 2018Review
- Development of dual casein kinase 1δ/1ε (CK1δ/ε) inhibitors for treatment of breast cancer.Bioorganic & medicinal chemistry · 2018Article
- Combined Virtual and Experimental Screening for CK1 Inhibitors Identifies a Modulator of p53 and Reveals Important Aspects of in Silico Screening Performance.International journal of molecular sciences · 2017Article
- Nuclear matrix protein SMAR1 represses c-Fos-mediated HPV18 E6 transcription through alteration of chromatin histone deacetylation.The Journal of biological chemistry · 2014Article
- Nek2 phosphorylates and stabilizes β-catenin at mitotic centrosomes downstream of Plk1.Molecular biology of the cell · 2014Article
- The CK1 Family: Contribution to Cellular Stress Response and Its Role in Carcinogenesis.Frontiers in oncology · 2014Review
- Pharmacological assessment defines Leishmania donovani casein kinase 1 as a drug target and reveals important functions in parasite viability and intracellular infection.Antimicrobial agents and chemotherapy · 2014Article
- Development of highly selective casein kinase 1δ/1ε (CK1δ/ε) inhibitors with potent antiproliferative properties.Bioorganic & medicinal chemistry letters · 2013Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
The tumor suppressor protein p53 is activated by distinct cellular stresses including radiation, hypoxia, type I interferon, and DNA/RNA virus infection. The transactivation domain of p53 contains a phosphorylation site at Ser20 whose modification stabilizes the binding of the transcriptional co-activator p300 and whose mutation in murine transgenics induces B-cell lymphoma. Although the checkpoint kinase CHK2 is implicated in promoting Ser20 site phosphorylation after irradiation, the enzyme that triggers this phosphorylation after DNA viral infection is undefined. Using human herpesvirus 6B (HHV-6B) as a virus that induces Ser20 site phosphorylation of p53 in T-cells, we sought to identify the kinase responsible for this virus-induced p53 modification. The p53 Ser20 kinase was fractionated and purified using cation, anion, and dye-ligand exchange chromatography. Mass spectrometry identified casein kinase 1 (CK1) and vaccinia-related kinase 1 (VRK1) as enzymes that coeluted with virus-induced Ser20 site kinase activity. Immunodepletion of CK1 but not VRK1 removed the kinase activity from the peak fraction, and bacterially expressed CK1 exhibited Ser20 site kinase activity equivalent to that of the virus-induced native CK1. CK1 modified p53 in a docking-dependent manner, which is similar to other known Ser20 site p53 kinases. Low levels of the CK1 inhibitor D4476 selectively inhibited HHV-6B-induced Ser20 site phosphorylation of p53. However, x-ray-induced Ser20 site phosphorylation of p53 was not blocked by D4476. These data highlight a central role for CK1 as the Ser20 site kinase for p53 in DNA virus-infected cells but also suggest that distinct stresses may selectively trigger different protein kinases to modify the transactivation domain of p53 at Ser20.
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