Evidence map›Paper›PMID 12941894›Full record

ArticleJournal of virology2003

Human papillomavirus type 16 E6 activates TERT gene transcription through induction of c-Myc and release of USF-mediated repression.

H R McMurray, D J McCance

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

81 citing papers in PubMed, 166 citations in OpenAlex.

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21 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 1 country.

H R McMurrayDepartment of Microbiology and Immunology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
D J McCance
University of Rochester · US

Funding

CO-ACTIVATOR FUNCTION IN ORAL CANCER CELLSR01DE013526 · NIDCR · UNIVERSITY OF ROCHESTER · PI MCCANCE, DENNIS J. · 2000 to 2004
$1.4M
Training Program in Oral Infectious DiseasesT32DE007165 · NIDCR · UNIVERSITY OF ROCHESTER · PI QUIVEY, ROBERT G · 1985 to 2005
$1.2M
NIDCR NIH HHS DE 13526NIDCR NIH HHS R01 DE013526NIDCR NIH HHS T32 DE007165NIDCR NIH HHS T32 DE 07165
6 · The paper itself

Abstract

Human papillomavirus type 16 (HPV-16), a DNA tumor virus, has a causal role in cervical cancer, and the viral oncoproteins E6 and E7 contribute to oncogenesis in multiple ways. E6 increases telomerase activity in keratinocytes through increased transcription of the telomerase catalytic subunit gene (TERT), but the factors involved in this have been elusive. We have found that mutation of the proximal E box in the TERT promoter has an activating effect in luciferase assays. This suggested that a repressive complex might be present at this site. HPV-16 E6 activated the TERT promoter predominantly through the proximal E box, and thus, might be acting on this repressive complex. This site is specific for the Myc/Mad/Max transcription factors as well as USF1 and USF2. Addition of exogenous USF1 or USF2 repressed activation of the TERT promoter by E6, dependent on the proximal E box. Using siRNA against USF1 or USF2 allowed for greater activation of the TERT promoter by E6. Conversely, loss of c-Myc function, through a dominant-negative Myc molecule, reduced activation by E6. Chromatin immunoprecipitations showed that in the presence of E6, there was a reduction in binding of USF1 and USF2 at the TERT promoter proximal E box, and a concomitant increase in c-Myc bound to this site. This shows that a repressive complex containing USF1 and USF2 is present in normal cells with little or no telomerase activity. In E6 keratinocytes, this repressive complex is replaced by c-Myc, which corresponds to higher levels of TERT transcription and consequently, telomerase activity.

Indexed as

DNA-Binding ProteinsGene Expression RegulationCells, CulturedHumansKeratinocytesOncogene Proteins, ViralPromoter Regions, GeneticProto-Oncogene Proteins c-mycRepressor ProteinsRNA, Small InterferingTelomeraseTranscription FactorsTranscription, GeneticUpstream Stimulatory FactorsDNA-Binding ProteinsE6 protein, Human papillomavirus type 16Oncogene Proteins, ViralProto-Oncogene Proteins c-mycRepressor ProteinsRNA, Small InterferingTelomeraseTERT protein, humanTranscription FactorsUpstream Stimulatory FactorsUSF1 protein, humanUSF2 protein, human

Identifiers

PMID12941894
PMCPMC224601
OpenAlexW2046002864

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.