Evidence map›Paper›PMID 26216987›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2015

Role of ubiquitin and the HPV E6 oncoprotein in E6AP-mediated ubiquitination.

Franziska Mortensen, Daniel Schneider, Tanja Barbic, Anna Sladewska-Marquardt, Simone Kühnle, Andreas Marx, Martin Scheffner

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

41 citing papers in PubMed, 53 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. HPV16 E6 oncoprotein promotes microhomology-mediated viral integration by increasing PolΘ protein expression.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  6. Review
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Mechanistic basis for ubiquitin modulation of a protein energy landscape.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  18. Article
  19. Adaptors as the regulators of HECT ubiquitin ligases.Cell death and differentiation · 2021
    Review
  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

7 authors at 1 institution in 1 country.

Franziska MortensenDepartment of Biology, University of Konstanz, 78457 Konstanz, Germany; Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany;
Daniel SchneiderDepartment of Biology, University of Konstanz, 78457 Konstanz, Germany; Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany.
Tanja BarbicDepartment of Biology, University of Konstanz, 78457 Konstanz, Germany;
Anna Sladewska-MarquardtDepartment of Biology, University of Konstanz, 78457 Konstanz, Germany;
Simone KühnleDepartment of Biology, University of Konstanz, 78457 Konstanz, Germany;
Andreas MarxKonstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany; Department of Chemistry, University of Konstanz, 78457 Konstanz, Germany.
Martin ScheffnerDepartment of Biology, University of Konstanz, 78457 Konstanz, Germany; Konstanz Research School Chemical Biology, University of Konstanz, 78457 Konstanz, Germany; martin.scheffner@uni-konstanz.de.
University of Konstanz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Deregulation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with three different clinical pictures. Hijacking of E6AP by the E6 oncoprotein of distinct human papillomaviruses (HPV) contributes to the development of cervical cancer, whereas loss of E6AP expression or function is the cause of Angelman syndrome, a neurodevelopmental disorder, and increased expression of E6AP has been involved in autism spectrum disorders. Although these observations indicate that the activity of E6AP has to be tightly controlled, only little is known about how E6AP is regulated at the posttranslational level. Here, we provide evidence that the hydrophobic patch of ubiquitin comprising Leu-8 and Ile-44 is important for E6AP-mediated ubiquitination, whereas it does not affect the catalytic properties of the isolated catalytic HECT domain of E6AP. Furthermore, we show that the HPV E6 oncoprotein rescues the disability of full-length E6AP to use a respective hydrophobic patch mutant of ubiquitin for ubiquitination and that it stimulates E6AP-mediated ubiquitination of Ring1B, a known substrate of E6AP, in vitro and in cells. Based on these data, we propose that E6AP exists in at least two different states, an active and a less active or latent one, and that the activity of E6AP is controlled by noncovalent interactions with ubiquitin and allosteric activators such as the HPV E6 oncoprotein.

Indexed as

UbiquitinationAllosteric RegulationAmino Acid SequenceBiocatalysisCell Line, TumorCysteineHumansHydrophobic and Hydrophilic InteractionsMolecular Sequence DataPeptidesProtein BindingProtein Structure, TertiaryUbiquitinUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesCysteinePeptidesUBE2D2 protein, humanUBE2L3 protein, humanUBE3A protein, humanUbiquitinUbiquitin-Conjugating EnzymesUbiquitin-Protein LigasesAngelman syndromeE6AP/UBE3AE6 oncoproteinhuman papillomavirusubiquitin

Identifiers

PMID26216987
PMCPMC4538620
OpenAlexW1935118997

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.