Evidence map›Paper›PMID 18922873›Full record

ArticleJournal of virology2009

Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding.

Jennifer Hein, Sergei Boichuk, Jiaping Wu, Yuan Cheng, Raimundo Freire, Parmjit S Jat, Thomas M Roberts, Ole V Gjoerup

Abstract read
In one paragraph

Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.

0numbers the graph read from it
0cells of the map it votes in
79citing papers in PubMed
3.9field-weighted citation impact, top 6% 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

79 citing papers in PubMed, 129 citations in OpenAlex.

  1. Review
  2. Article
  3. Claspin and Cancer: Where Are We Now?International journal of molecular sciences · 2025
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  10. Transcriptomic analysis of the innate immune response toMolecular therapy. Nucleic acids · 2023
    Article
  11. Article
  12. Article
  13. Zombies Never Die: The Double Life Bub1 Lives in Mitosis.Frontiers in cell and developmental biology · 2022
    Review
  14. Review
  15. Article
  16. Article
  17. Immortalization of primary sheep embryo kidney cells.In vitro cellular & developmental biology. Animal · 2021
    Article
  18. Article
  19. Article
  20. Review

19 more citing papers are in PubMed but not listed here.

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

8 authors at 5 institutions in 3 countries.

Jennifer HeinHillman Cancer Center, Research Pavilion Suite 1.8, 5117 Centre Avenue, Pittsburgh, PA 15213, USA. ovg27@pitt.edu
Sergei Boichuk
Jiaping Wu
Yuan Cheng
Raimundo Freire
Parmjit S Jat
Thomas M Roberts
Ole V Gjoerup
UPMC Hillman Cancer Center · USHarvard University · USDana-Farber Cancer Institute · USHospital Universitario de Canarias · ESUniversity College London · GB

Funding

VIRAL ONCOPROTEIN PERTURBATION OF RB/E2F PATHWAYP01CA050661 · NCI · DANA-FARBER CANCER INSTITUTE · PI HOWLEY, PETER M · 1989 to 2013
$35.8M
MOLECULAR MECHANISMS OF POLYOMA INDUCED TRANSFORMATIONR01CA030002 · NCI · DANA-FARBER CANCER INSTITUTE · PI ROBERTS, THOMAS M · 1985 to 2014
$5.8M
MOLECULAR MECHANISMS OF POLYOMA-INDUCED TRANSFORMATIONR37CA030002 · NCI · DANA-FARBER CANCER INSTITUTE · PI ROBERTS, THOMAS M · 1993 to 1999
–
NCI NIH HHS CA30002NCI NIH HHS P01 CA050661NCI NIH HHS P01-CA50661NCI NIH HHS R01 CA030002NCI NIH HHS R37 CA030002Wellcome TrustWellcome Trust 072672Wellcome Trust 078305
6 · The paper itself

Abstract

Simian virus 40 (SV40) large T antigen (LT) is a multifunctional protein that is important for viral replication and oncogenic transformation. Previously, infection of monkey or human cells with SV40 was shown to lead to the induction of DNA damage response signaling, which is required for efficient viral replication. However, it was not clear if LT is sufficient to induce the damage response and, if so, what the genetic requirements and functional consequences might be. Here, we show that the expression of LT alone, without a replication origin, can induce key DNA damage response markers including the accumulation of gamma-H2AX and 53BP1 in nuclear foci. Other DNA damage-signaling components downstream of ATM/ATR kinases were induced, including chk1 and chk2. LT also bound the Claspin mediator protein, which normally facilitates the ATR activation of chk1 and monitors cellular replication origins. Stimulation of the damage response by LT depends mainly on binding to Bub1 rather than to the retinoblastoma protein. LT has long been known to stabilize p53 despite functionally inactivating it. We show that the activation of a DNA damage response by LT via Bub1 appears to play a major role in p53 stabilization by promoting the phosphorylation of p53 at Ser15. Accompanying the DNA damage response, LT induces tetraploidy, which is also dependent on Bub1 binding. Taken together, our data suggest that LT, via Bub1 binding, breaches genome integrity mechanisms, leading to DNA damage responses, p53 stabilization, and tetraploidy.

Indexed as

DNA DamageDNA RepairAdaptor Proteins, Signal TransducingAntigens, Polyomavirus TransformingCell LineCheckpoint Kinase 1Checkpoint Kinase 2HistonesHumansIntracellular Signaling Peptides and ProteinsPolyploidyProtein BindingProtein KinasesProtein Serine-Threonine KinasesSimian virus 40Tumor Suppressor Protein p53Adaptor Proteins, Signal TransducingAntigens, Polyomavirus TransformingBUB1 protein, humanBub1 spindle checkpoint proteinCheckpoint Kinase 1Checkpoint Kinase 2CHEK1 protein, humanCHEK2 protein, humanHistonesIntracellular Signaling Peptides and ProteinsProtein KinasesProtein Serine-Threonine KinasesTumor Suppressor Protein p53

Identifiers

PMID18922873
PMCPMC2612341
OpenAlexW2122969156

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.