Evidence map›Paper›PMID 23592995›Full record

ArticlePLoS pathogens2013

HPV16 E7 protein and hTERT proteins defective for telomere maintenance cooperate to immortalize human keratinocytes.

Jonathan Miller, Aleksandra Dakic, Renxiang Chen, Nancy Palechor-Ceron, Yuhai Dai, Bhaskar Kallakury, Richard Schlegel, Xuefeng Liu

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

29 citing papers in PubMed, 44 citations in OpenAlex.

  1. Article
  2. The Rab5 effector Rabankyrin-5 mediates endosomal fusion and trafficking of human papillomavirus during early entry.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  14. Non-invasiveOncotarget · 2017
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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

8 authors at 2 institutions in 1 country.

Jonathan MillerDepartment of Pathology, Georgetown University Medical Center, Washington, D.C., United States of America.
Aleksandra Dakic
Renxiang Chen
Nancy Palechor-Ceron
Yuhai Dai
Bhaskar Kallakury
Richard Schlegel
Xuefeng Liu
Georgetown University · USGeorgetown University Medical Center · US

Funding

Tissue Culture Shared ResourceP30CA051008 · NCI · GEORGETOWN UNIVERSITY · PI STEPHEN W BYERS · 1990 to 2026
$71.5M
HPV E6 protein regulation of the hTERT promoterR01CA106400 · NCI · GEORGETOWN UNIVERSITY · PI SCHLEGEL, RICHARD · 2004 to 2008
$1.6M
NCI NIH HHS 5P30CA051008NCI NIH HHS P30 CA051008NCI NIH HHS R01 CA106400NCI NIH HHS R01CA106440
6 · The paper itself

Abstract

Previous studies have shown that wild-type human telomerase reverse transcriptase (hTERT) protein can functionally replace the human papillomavirus type 16 (HPV-16) E6 protein, which cooperates with the viral E7 protein in the immortalization of primary keratinocytes. In the current study, we made the surprising finding that catalytically inactive hTERT (hTERT-D868A), elongation-defective hTERT (hTERT-HA), and telomere recruitment-defective hTERT (hTERT N+T) also cooperate with E7 in mediating bypass of the senescence blockade and effecting cell immortalization. This suggests that hTERT has activities independent of its telomere maintenance functions that mediate transit across this restriction point. Since hTERT has been shown to have a role in gene activation, we performed microarray studies and discovered that E6, hTERT and mutant hTERT proteins altered the expression of highly overlapping sets of cellular genes. Most important, the E6 and hTERT proteins induced mRNA and protein levels of Bmi1, the core subunit of the Polycomb Group (PcG) complex 1. We show further that Bmi1 substitutes for E6 or hTERT in cell immortalization. Finally, tissue array studies demonstrated that expression of Bmi1 increased with the severity of cervical dysplasia, suggesting a potential role in the progression of cervical cancer. Together, these data demonstrate that hTERT has extra-telomeric activities that facilitate cell immortalization and that its induction of Bmi1 is one potential mechanism for mediating this activity.

Indexed as

Cell Transformation, ViralHuman papillomavirus 16HumansKeratinocytesOncogene Proteins, ViralPapillomavirus E7 ProteinsPolycomb Repressive Complex 1Promoter Regions, GeneticRepressor ProteinsRNA, MessengerTelomeraseTelomereBMI1 protein, humanE6 protein, Human papillomavirus type 16oncogene protein E7, Human papillomavirus type 16Oncogene Proteins, ViralPapillomavirus E7 ProteinsPolycomb Repressive Complex 1Repressor ProteinsRNA, MessengerTelomeraseTERT protein, human

Identifiers

PMID23592995
PMCPMC3617164
OpenAlexW2089360483

What OpenQuestion holds

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LicenceCC BY
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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.