Evidence map›Paper›PMID 22046250›Full record

ArticlePloS one2011

Proteasomal degradation of p53 by human papillomavirus E6 oncoprotein relies on the structural integrity of p53 core domain.

Xavier Bernard, Philip Robinson, Yves Nominé, Murielle Masson, Sebastian Charbonnier, Juan Ramon Ramirez-Ramos, Francois Deryckere, Gilles Travé, Georges Orfanoudakis

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

28 citing papers in PubMed, 52 citations in OpenAlex.

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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 1 country.

Xavier BernardOncoprotéines, UMR 7242 CNRS, Ecole Supérieure de Biotechnologie de Strasbourg, Université de Strasbourg, Illkirch, France.
Philip Robinson
Yves Nominé
Murielle Masson
Sebastian Charbonnier
Juan Ramon Ramirez-Ramos
Francois Deryckere
Gilles Travé
Georges Orfanoudakis
École Supérieure de Biotechnologie de Strasbourg · FRCentre National de la Recherche Scientifique · FRUniversité de Strasbourg · FRUniversité de Bordeaux · FR

Funding

Papillomavirus E6 Structural ConsortiumR01CA134737 · NCI · UNIVERSITY OF VIRGINIA · PI VANDE POL, SCOTT BRIAN · 2010 to 2019
$4.2M
NCI NIH HHS R01 CA134737
6 · The paper itself

Abstract

The E6 oncoprotein produced by high-risk mucosal HPV stimulates ubiquitinylation and proteasome-dependent degradation of the tumour suppressor p53 via formation of a trimeric complex comprising E6, p53, and E6-AP. p53 is also degraded by its main cellular regulator MDM2. The main binding site of p53 to MDM2 is situated in the natively unfolded N-terminal region of p53. By contrast, the regions of p53 implicated in the degradation by viral E6 are not fully identified to date. Here we generated a series of mutations (Y103G, Y107G, T155A, T155V, T155D, L264A, L265A) targeting the central folded core domain of p53 within a region opposite to its DNA-binding site. We analysed by in vitro and in vivo assays the impact of these mutations on p53 degradation mediated by viral E6 oncoprotein. Whereas all mutants remained susceptible to MDM2-mediated degradation, several of them (Y103G, Y107G, T155D, L265A) became resistant to E6-mediated degradation, confirming previous works that pointed to the core domain as an essential region for the degradation of p53. In parallel, we systematically checked the impact of the mutations on the transactivation activity of p53 as well as on the conformation of p53, analysed by Nuclear Magnetic Resonance (NMR), circular dichroism (CD), and antibody probing. These measurements suggested that the conformational integrity of the core domain is an essential parameter for the degradation of p53 by E6, while it is not essential for the degradation of p53 by MDM2. Thus, the intracellular stability of a protein may or may not rely on its biophysical stability depending on the degradation pathway taken into consideration.

Indexed as

Binding SitesHumansMutagenesis, Site-DirectedOncogene Proteins, ViralProteasome Endopeptidase ComplexProtein ConformationProtein StabilityProto-Oncogene Proteins c-mdm2Repressor ProteinsTumor Suppressor Protein p53E6 protein, Human papillomavirus type 16MDM2 protein, humanOncogene Proteins, ViralProteasome Endopeptidase ComplexProto-Oncogene Proteins c-mdm2Repressor ProteinsTP53 protein, humanTumor Suppressor Protein p53

Identifiers

PMID22046250
PMCPMC3203139
OpenAlexW1985349353

What OpenQuestion holds

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LicenceCC BY
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.