Evidence map›Paper›PMID 23093938›Full record

ArticlePLoS pathogens2012

Phosphorylation of the chromatin binding domain of KSHV LANA.

Crystal Woodard, Meir Shamay, Gangling Liao, Jian Zhu, Ai Na Ng, Renfeng Li, Rob Newman, Hee-Sool Rho, Jianfei Hu, Jun Wan and 3 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

28 citing papers in PubMed, 34 citations in OpenAlex.

  1. Review
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  15. Kaposi's Sarcoma Herpesvirus Genome Persistence.Frontiers in microbiology · 2016
    Review
  16. 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

13 authors at 4 institutions in 2 countries.

Crystal WoodardHigh Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Meir Shamay
Gangling Liao
Jian Zhu
Ai Na Ng
Renfeng Li
Rob Newman
Hee-Sool Rho
Jianfei Hu
Jun Wan
Jiang Qian
Heng Zhu
S Diane Hayward
Johns Hopkins University · USJohns Hopkins Medicine · USHigh Throughput Biology (United States) · USUniversity of Bristol · GB

Funding

TCP5: ACTIVE SITE LABELING REAGENT FOR ACETYLTRANSFERASESU54RR020839 · NCRR · JOHNS HOPKINS UNIVERSITY · PI BOEKE, JEF D · 2004 to 2011
$27.4M
Networks, Pathways and Dynamics of Lysine ModificationU54GM103520 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI BADER, JOEL S. · 2012 to 2013
$7.0M
Role of KSHV in AIDS MalignanciesP01CA113239 · NCI · JOHNS HOPKINS UNIVERSITY · PI NICHOLAS, JOHN · 2006 to 2010
$5.8M
DNA-Binding Activity of Human Transcription FactorsR01GM076102 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI ZHU, HENG · 2006 to 2014
$2.6M
MANIPULATION OF KINASE ACTIVITY BY KSHV LANAR21CA138163 · NCI · JOHNS HOPKINS UNIVERSITY · PI HAYWARD, S DIANE · 2009 to 2010
$397k
NCI NIH HHS P01 CA113239NCI NIH HHS P01CA113239NCI NIH HHS R21 CA138163NCI NIH HHS R21CA138163NCRR NIH HHS RR020839NCRR NIH HHS U54 RR020839NIGMS NIH HHS GM076102NIGMS NIH HHS R01 GM076102NIGMS NIH HHS U54 GM103520
6 · The paper itself

Abstract

The Kaposi sarcoma associated herpesvirus (KSHV) latency associated nuclear antigen (LANA) is expressed in all KSHV associated malignancies and is essential for maintenance of KSHV genomes in infected cells. To identify kinases that are potentially capable of modifying LANA, in vitro phosphorylation assays were performed using an Epstein Barr virus plus LANA protein microarray and 268 human kinases purified in active form from yeast. Interestingly, of the Epstein-Barr virus proteins on the array, the EBNA1 protein had the most similar kinase profile to LANA. We focused on nuclear kinases and on the N-terminus of LANA (amino acids 1-329) that contains the LANA chromatin binding domain. Sixty-three nuclear kinases phosphorylated the LANA N-terminus. Twenty-four nuclear kinases phosphorylated a peptide covering the LANA chromatin binding domain (amino acids 3-21). Alanine mutations of serine 10 and threonine 14 abolish or severely diminish chromatin and histone binding by LANA. However, conversion of these residues to the phosphomimetic glutamic acid restored histone binding suggesting that phosphorylation of serine 10 and threonine 14 may modulate LANA function. Serine 10 and threonine 14 were validated as substrates of casein kinase 1, PIM1, GSK-3 and RSK3 kinases. Short-term treatment of transfected cells with inhibitors of these kinases found that only RSK inhibition reduced LANA interaction with endogenous histone H2B. Extended treatment of PEL cell cultures with RSK inhibitor caused a decrease in LANA protein levels associated with p21 induction and a loss of PEL cell viability. The data indicate that RSK phosphorylation affects both LANA accumulation and function.

Indexed as

Amino Acid SequenceAntigens, ViralBinding SitesCasein Kinase ICell LineChromatinFungal ProteinsGlycogen Synthase Kinase 3HEK293 CellsHerpesvirus 4, HumanHerpesvirus 8, HumanHistonesHumansMitogen-Activated Protein KinasesNuclear ProteinsPhosphorylationAntigens, ViralCasein Kinase IChromatinFungal ProteinsGlycogen Synthase Kinase 3Histoneslatency-associated nuclear antigenMitogen-Activated Protein KinasesNuclear ProteinsPim1 protein, Pichia pastorisProtein Kinasesribosomal protein S6 kinase, 90kDa, polypeptide 3Ribosomal Protein S6 Kinases, 90-kDa

Identifiers

PMID23093938
PMCPMC3475679
OpenAlexW2052268346

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.