Evidence map›Paper›PMID 26405826›Full record

ArticlePLoS pathogens2015

The Deacetylase Sirtuin 1 Regulates Human Papillomavirus Replication by Modulating Histone Acetylation and Recruitment of DNA Damage Factors NBS1 and Rad51 to Viral Genomes.

Erika S Langsfeld, Jason M Bodily, Laimonis A Laimins

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed
4.3field-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

53 citing papers in PubMed, 87 citations in OpenAlex.

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  13. Article
  14. A DeacetylaseViruses · 2022
    Article
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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

3 authors at 2 institutions in 1 country.

Erika S LangsfeldDepartment of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States of America.
Jason M BodilyDepartment of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, Louisiana, United States of America.
Laimonis A LaiminsDepartment of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, United States of America.
Northwestern University · USLouisiana State University Health Sciences Center Shreveport · US

Funding

Tumor Environment and Metastasis (TEAM) Research ProgramP30CA060553 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Daniela E Matei · 1993 to 2026
$153.9M
REGULATION OF HUMAN PAPILLOMAVIRUS GENE EXPRESSIONR01CA059655 · NCI · UNIVERSITY OF CHICAGO · PI LAIMINS, LAIMONIS A. · 1993 to 2023
$7.4M
The Role of Keratinocytes as Independent ThermosensorsP30AR057216 · NIAMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PALLER, AMY S · 2009 to 2018
$6.0M
Renewal: HPV and the DNA Damage ResponseR01CA142861 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI Laimonis A. LAIMINS · 2010 to 2026
$5.2M
ThThe Role of Epithelial-Stromal Communication in the Human Papillomavirus Type 16 Life CycleR01AI118904 · NIAID · LOUISIANA STATE UNIV HSC SHREVEPORT · PI BODILY, JASON M · 2015 to 2019
$1.6M
Training Program in Viral ReplicationT32AI060523 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI LAIMINS, LAIMONIS A. · 2004 to 2013
$1.4M
NCI NIH HHS P30 CA060553NCI NIH HHS R01 CA059655NCI NIH HHS R01 CA142861NCI NIH HHS R01CA142861NCI NIH HHS R01CA59655NIAID NIH HHS R01 AI118904NIAID NIH HHS T31AI60523NIAID NIH HHS T32 AI060523NIAMS NIH HHS P30 AR057216
6 · The paper itself

Abstract

Human papillomaviruses (HPV) regulate their differentiation-dependent life cycles by activating a number of cellular pathways, such as the DNA damage response, through control of post-translational protein modification. Sirtuin 1 (SIRT1) is a protein deacetylase that modulates the acetylation of a number of cellular substrates, resulting in activation of pathways controlling gene expression and DNA damage repair. Our studies indicate that SIRT1 levels are increased in cells containing episomes of high-risk HPV types through the combined action of the E6 and E7 oncoproteins. Knockdown of SIRT1 in these cells with shRNAs impairs viral activities including genome maintenance, amplification and late gene transcription, with minimal effects on cellular proliferation ability. Abrogation of amplification was also seen following treatment with the SIRT1 deacetylase inhibitor, EX-527. Importantly, SIRT1 binds multiple regions of the HPV genome in undifferentiated cells, but this association is lost upon of differentiation. SIRT1 regulates the acetylation of Histone H1 (Lys26) and H4 (Lys16) bound to HPV genomes and this may contribute to regulation of viral replication and gene expression. The differentiation-dependent replication of high-risk HPVs requires activation of factors in the Ataxia Telangiectasia Mutated (ATM) pathway and SIRT1 regulates the recruitment of both NBS1 and Rad51 to the viral genomes. These observations demonstrate that SIRT1 is a critical regulator of multiple aspects of the high-risk HPV life cycle.

Indexed as

AcetylationBlotting, WesternCell Cycle ProteinsCells, CulturedChromatin ImmunoprecipitationFluorescent Antibody TechniqueHistonesHumansImmunoblottingLife Cycle StagesNuclear ProteinsPapillomaviridaePapillomavirus InfectionsRad51 RecombinaseRNA, Small InterferingSirtuin 1Cell Cycle ProteinsHistonesNBN protein, humanNuclear ProteinsRAD51 protein, humanRad51 RecombinaseRNA, Small InterferingSIRT1 protein, humanSirtuin 1

Identifiers

PMID26405826
PMCPMC4583417
OpenAlexW1684802335

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.