Evidence map›Paper›PMID 18669630›Full record

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.

Nicola J MacLaine, Bodil Oster, Bettina Bundgaard, Jennifer A Fraser, Carolyn Buckner, Pedro A Lazo, David W Meek, Per Höllsberg, Ted R Hupp

Open access · hybridAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.1field-weighted citation impact, top 13% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Targeting Protein Kinases in Blood Cancer: Focusing on CK1α and CK2.International journal of molecular sciences · 2021
    Review
  9. Article
  10. Article
  11. Review
  12. Article
  13. Casein kinase 1α: biological mechanisms and theranostic potential.Cell communication and signaling : CCS · 2018
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

Nicola J MacLaineUniversity of Edinburgh, Crewe Road South, Edinburgh, EH4 2XR, United Kingdom.
Bodil Oster
Bettina Bundgaard
Jennifer A Fraser
Carolyn Buckner
Pedro A Lazo
David W Meek
Per Höllsberg
Ted R Hupp
Edinburgh Cancer Research · GBAarhus University · DKNinewells Hospital · GBUniversidad de Salamanca · ES

Funding

Biotechnology and Biological Sciences Research CouncilCancer Research UK
6 · The paper itself

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.

Indexed as

Amino Acid SequenceAntiviral AgentsCasein Kinase ICatalysisCell Line, TumorHerpesvirus 6, HumanHumansMass SpectrometryMolecular Sequence DataPhosphorylationProtein Structure, TertiaryRoseolovirus InfectionsSerineTranscriptional ActivationTumor Suppressor Protein p53Antiviral AgentsCasein Kinase ISerineTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID18669630
PMCPMC2661408
OpenAlexW2100674208

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.