Evidence map›Paper›PMID 20631133›Full record

ArticleJournal of virology2010

The human papillomavirus type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis.

Jennifer M Spangle, Karl Münger

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

Article in Journal of virology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
125citing papers in PubMed, 2 pooled it
5.3field-weighted citation impact, top 3% 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

125 citing papers in PubMed, 2 syntheses or guidelines pooled it, 199 citations in OpenAlex.

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65 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 2 institutions in 1 country.

Jennifer M SpangleDivision of Infectious Diseases, Brigham and Women's Hospital and Committee on Virology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Karl Münger
Brigham and Women's Hospital · USHarvard University · US

Funding

MODULATION OF HOST CELL APOPTOTIC RESPONSES BY HPVE7R01CA081135 · NCI · TUFTS UNIVERSITY BOSTON · PI MUNGER, KARL · 2000 to 2014
$4.2M
VIRUS-HOST INTERACTIONS IN CANCERT32CA009031 · NCI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI KIEFF, ELLIOTT D · 1985 to 2009
$2.4M
NCI NIH HHS R01 CA081135NCI NIH HHS R01CA081135NCI NIH HHS T32 CA009031NCI NIH HHS T32CA009031
6 · The paper itself

Abstract

The mammalian target of rapamycin (mTOR) kinase acts as a cellular rheostat that integrates signals from a variety of cellular signal transduction pathways that sense growth factor and nutrient availability as well as intracellular energy status. It was previously reported that the human papillomavirus type 16 (HPV16) E6 oncoprotein may activate the S6 protein kinase (S6K) through binding and E6AP-mediated degradation of the mTOR inhibitor tuberous sclerosis complex 2 (TSC2) (Z. Lu, X. Hu, Y. Li, L. Zheng, Y. Zhou, H. Jiang, T. Ning, Z. Basang, C. Zhang, and Y. Ke, J. Biol. Chem. 279:35664-35670, 2004; L. Zheng, H. Ding, Z. Lu, Y. Li, Y. Pan, T. Ning, and Y. Ke, Genes Cells 13:285-294, 2008). Our results confirmed that HPV16 E6 expression causes an increase in mTORC1 activity through enhanced phosphorylation of mTOR and activation of downstream signaling pathways S6K and eukaryotic initiation factor binding protein 1 (4E-BP1). However, we did not detect a decrease in TSC2 levels in HPV16 E6-expressing cells. We discovered, however, that HPV16 E6 expression causes AKT activation through the upstream kinases PDK1 and mTORC2 under conditions of nutrient deprivation. We show that HPV16 E6 expression causes an increase in protein synthesis by enhancing translation initiation complex assembly at the 5' mRNA cap and an increase in cap-dependent translation. The increase in cap-dependent translation likely results from HPV16 E6-induced AKT/mTORC1 activation, as the assembly of the translation initiation complex and cap-dependent translation are rapamycin sensitive. Lastly, coexpression of the HPV16 E6 and E7 oncoproteins does not affect HPV16 E6-induced activation of mTORC1 and cap-dependent translation. HPV16 E6-mediated activation of mTORC1 signaling and cap-dependent translation may be a mechanism to promote viral replication under conditions of limited nutrient supply in differentiated, HPV oncoprotein-expressing proliferating cells.

Indexed as

Peptide Chain Initiation, TranslationalSignal TransductionCell LineHost-Pathogen InteractionsHumansKeratinocytesMechanistic Target of Rapamycin Complex 1Multiprotein ComplexesOncogene Proteins, ViralOncogene Protein v-aktPhosphorylationProteinsProtein Serine-Threonine KinasesPyruvate Dehydrogenase Acetyl-Transferring KinaseRepressor ProteinsTOR Serine-Threonine KinasesCRTC2 protein, humanE6 protein, Human papillomavirus type 16Mechanistic Target of Rapamycin Complex 1Multiprotein ComplexesOncogene Proteins, ViralOncogene Protein v-aktPDK1 protein, humanProteinsProtein Serine-Threonine KinasesPyruvate Dehydrogenase Acetyl-Transferring KinaseRepressor ProteinsTOR Serine-Threonine KinasesTranscription Factors

Identifiers

PMID20631133
PMCPMC2937655
OpenAlexW2138216581

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.