Evidence map›Paper›PMID 19553317›Full record

ArticleJournal of virology2009

Brd4 regulation of papillomavirus protein E2 stability.

Gang Zheng, Michal-Ruth Schweiger, Gustavo Martinez-Noel, Leon Zheng, Jennifer A Smith, J Wade Harper, Peter M Howley

Open access · greenAbstract 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 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

35 citing papers in PubMed, 50 citations in OpenAlex.

  1. Journal of virology · 2026
    Article
  2. bioRxiv : the preprint server for biology · 2025
    Article
  3. E2 Tyrosine 102 Regulates MmuPV1 Pathogenesis In Vivo.Pathogens (Basel, Switzerland) · 2025
    Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. HPV disease transmission protection and control.Microbial cell (Graz, Austria) · 2016
    Review
  17. Article
  18. Article
  19. Article
  20. Review
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

7 authors at 1 institution in 1 country.

Gang ZhengDepartment of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Michal-Ruth Schweiger
Gustavo Martinez-Noel
Leon Zheng
Jennifer A Smith
J Wade Harper
Peter M Howley
Harvard University · US

Funding

Ubiquitin Mediated Proteolysis and Cell Cycle ControlR01AG011085 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JEFFREY W HARPER · 1993 to 2026
$10.9M
Tumor Cell Biology Training ProgramT32CA009361 · NCI · DANA-FARBER CANCER INSTITUTE · PI GRAY, NATHANAEL SCHIANDER · 1985 to 2015
$8.9M
SYSTEMATIC ANALYSIS OF THE DUB PROTEOMER01GM054137 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI HARPER, JEFFREY W · 1996 to 2012
$4.1M
Papillomavirus E2 Functions: Cellular Regulation and EffectorsR01CA116720 · NCI · HARVARD MEDICAL SCHOOL · PI HOWLEY, PETER M · 2006 to 2015
$2.8M
SYSTEMATIC ANALYSIS OF PROTEOLYSIS PATHWAYS FOR CULLIN TARGETSR01GM070565 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI HARPER, JEFFREY W · 2005 to 2012
$2.6M
NCI NIH HHS R01 CA116720NCI NIH HHS R01CA116720NCI NIH HHS T32 CA009361NCI NIH HHS T32CA009361-27NIA NIH HHS R01 AG011085NIA NIH HHS R01AG011085NIGMS NIH HHS R01 GM054137NIGMS NIH HHS R01 GM070565NIGMS NIH HHS R01GM070565
6 · The paper itself

Abstract

The papillomavirus (PV) E2 protein is an important regulator of the viral life cycle. It has diverse roles in viral transcription, DNA replication, and genome maintenance. Our laboratory has previously identified the cellular bromodomain protein Brd4 as a key interacting partner of E2. Brd4 mediates the transcriptional activation function of E2 and plays an important role in viral genome maintenance in dividing cells. E2 interacts with the C-terminal domain (CTD) of Brd4, and the CTD functions in a dominant-negative manner through binding E2 and interfering with E2's interaction with the full-length Brd4 protein. Previous studies have shown that PV E2 proteins are short lived; however, the mechanisms regulating their stability and degradation have not yet been well established. In this study, we explored the role of Brd4 in the regulation of bovine PV 1 (BPV1) and human PV 16 (HPV16) E2 stability. Expression of the Brd4 CTD dramatically increases E2 levels. Both BPV1 E2 and HPV16 E2 are regulated by ubiquitylation, and Brd4 CTD expression blocks this ubiquitylation, thus stabilizing the E2 protein. Furthermore, we have identified the cullin-based E3 ligases and specifically cullin-3 as potential components of the ubiquitylation machinery that targets both BPV1 and HPV16 E2 for ubiquitylation. Expression of the Brd4 CTD blocks the interaction between E2 and the cullin-3 complex. In addition to Brd4's role in mediating E2 transcription and genome tethering activities, these data suggest a potential role for Brd4 in regulating E2 stability and protein levels within PV-infected cells.

Indexed as

AnimalsBovine papillomavirus 1Bromodomain Containing ProteinsCattleCell Cycle ProteinsCullin ProteinsDNA-Binding ProteinsHuman papillomavirus 16HumansNuclear ProteinsOncogene Proteins, ViralProtein StabilityTranscription FactorsUbiquitinationViral ProteinsBRD4 protein, humanBromodomain Containing ProteinsCell Cycle ProteinsCUL3 protein, humanCullin ProteinsDNA-Binding ProteinsE2 protein, Bovine papillomavirusNuclear Proteinsoncogene protein E2, Human papillomavirus type 1Oncogene Proteins, ViralTranscription FactorsViral Proteins

Identifiers

PMID19553317
PMCPMC2738164
OpenAlexW2130039951

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.