Evidence map›Paper›PMID 35608342›Full record

ArticleMicrobiology spectrum2022

A Critical Role for p53 during the HPV16 Life Cycle.

Christian T Fontan, Claire D James, Apurva T Prabhakar, Molly L Bristol, Raymonde Otoa, Xu Wang, Elmira Karimi, Pavithra Rajagopalan, Devraj Basu, Iain M Morgan

Open access · goldAbstract read
In one paragraph

Article in Microbiology spectrum, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
4.2field-weighted citation impact, top 5% 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

18 citing papers in PubMed, 30 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

10 authors at 3 institutions in 1 country.

Christian T FontanPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth Universitygrid.224260.0 (VCU), Richmond, Virginia, USA.
Claire D JamesPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth Universitygrid.224260.0 (VCU), Richmond, Virginia, USA.
Apurva T PrabhakarPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth Universitygrid.224260.0 (VCU), Richmond, Virginia, USA.
Molly L BristolPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth Universitygrid.224260.0 (VCU), Richmond, Virginia, USA.
Raymonde OtoaPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth Universitygrid.224260.0 (VCU), Richmond, Virginia, USA.
Xu WangPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth Universitygrid.224260.0 (VCU), Richmond, Virginia, USA.
Elmira KarimiPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth Universitygrid.224260.0 (VCU), Richmond, Virginia, USA.
Pavithra RajagopalanDepartment of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Devraj BasuDepartment of Otorhinolaryngology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Iain M MorganPhilips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth Universitygrid.224260.0 (VCU), Richmond, Virginia, USA.ORCID 0000-0002-4949-3032
Virginia Commonwealth University · USThe Wistar Institute · USUniversity of Pennsylvania · US

Funding

Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Kim Felder Rhoads · 1985 to 2026
$51.0M
JARID1B-mediated epigenetic regulation of oncogenic signals in oral cancerR01DE027185 · NIDCR · UNIVERSITY OF PENNSYLVANIA · PI BASU, DEVRAJ · 2018 to 2021
$1.5M
NCI NIH HHS P30 CA016059NIDCR NIH HHS R01 DE027185
6 · The paper itself

Abstract

Human papillomaviruses (HPV) are causative agents in ano-genital and oral cancers; HPV16 is the most prevalent type detected in human cancers. The HPV16 E6 protein targets p53 for proteasomal degradation to facilitate proliferation of the HPV16 infected cell. However, in HPV16 immortalized cells E6 is predominantly spliced (E6*) and unable to degrade p53. Here, we demonstrate that human foreskin keratinocytes immortalized by HPV16 (HFK+HPV16), and HPV16 positive oropharyngeal cancers, retain significant expression of p53. In addition, p53 levels increase in HPV16+ head and neck cancer cell lines following treatment with cisplatin. Introduction of full-length E6 into HFK+HPV16 resulted in attenuation of cellular growth (in hTERT immortalized HFK, E6 expression promoted enhanced proliferation). An understudied interaction is that between E2 and p53 and we investigated whether this was important for the viral life cycle. We generated mutant genomes with E2 unable to interact with p53 resulting in profound phenotypes in primary HFK. The mutant induced hyper-proliferation, but an ultimate arrest of cell growth; β-galactosidase staining demonstrated increased senescence, and COMET assays showed increased DNA damage compared with HFK+HPV16 wild-type cells. There was failure of the viral life cycle in organotypic rafts with the mutant HFK resulting in premature differentiation and reduced proliferation. The results demonstrate that p53 expression is critical during the HPV16 life cycle, and that this may be due to a functional interaction between E2 and p53. Disruption of this interaction has antiviral potential.

Indexed as

Oncogene Proteins, ViralPapillomavirus InfectionsAnimalsHuman papillomavirus 16HumansLife Cycle StagesPapillomaviridaeTumor Suppressor Protein p53Oncogene Proteins, ViralTumor Suppressor Protein p53cervical cancercometcomet assaydna bindingdna damageE2head and neck cancerhuman papillomavirusinteractionlife cyclep53papillomavirussenescence

Identifiers

PMID35608342
PMCPMC9241828
OpenAlexW4281383272

What OpenQuestion holds

Textmetadata
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.