Evidence map›Paper›PMID 24263171›Full record

ArticleBiochimica et biophysica acta2014

The Stress-response protein prostate-associated gene 4, interacts with c-Jun and potentiates its transactivation.

Krithika Rajagopalan, Ruoyi Qiu, Steven M Mooney, Shweta Rao, Takumi Shiraishi, Elizabeth Sacho, Hongying Huang, Ellen Shapiro, Keith R Weninger, Prakash Kulkarni

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

25 citing papers in PubMed, 39 citations in OpenAlex.

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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

10 authors at 3 institutions in 1 country.

Krithika RajagopalanDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Ruoyi QiuDepartment of Physics, North Carolina State University, Raleigh, NC 27695, USA.
Steven M MooneyDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Shweta RaoDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Takumi ShiraishiDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Elizabeth SachoDepartment of Physics, North Carolina State University, Raleigh, NC 27695, USA.
Hongying HuangDepartment of Urology, New York University School of Medicine, New York, NY 10016, USA.
Ellen ShapiroDepartment of Urology, New York University School of Medicine, New York, NY 10016, USA.
Keith R WeningerDepartment of Physics, North Carolina State University, Raleigh, NC 27695, USA. Electronic address: krwening@ncsu.edu.
Prakash KulkarniDepartment of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. Electronic address: pkulkar4@jhmi.edu.
Johns Hopkins University · USNorth Carolina State University · USNew York University · US

Funding

Translational Research Central ServicesP30CA006973 · NCI · JOHNS HOPKINS UNIVERSITY · PI Rosalie Wollett · 1985 to 2026
$208.6M
NCI NIH HHS P30 CA006973
6 · The paper itself

Abstract

The Cancer/Testis Antigen (CTA), Prostate-associated Gene 4 (PAGE4), is a stress-response protein that is upregulated in prostate cancer (PCa) especially in precursor lesions that result from inflammatory stress. In cells under stress, translocation of PAGE4 to mitochondria increases while production of reactive oxygen species decreases. Furthermore, PAGE4 is also upregulated in human fetal prostate, underscoring its potential role in development. However, the proteins that interact with PAGE4 and the mechanisms underlying its pleiotropic functions in prostatic development and disease remain unknown. Here, we identified c-Jun as a PAGE4 interacting partner. We show that both PAGE4 and c-Jun are overexpressed in the human fetal prostate; and in cell-based assays, PAGE4 robustly potentiates c-Jun transactivation. Single-molecule Förster resonance energy transfer experiments indicate that upon binding to c-Jun, PAGE4 undergoes conformational changes. However, no interaction is observed in presence of BSA or unilamellar vesicles containing the mitochondrial inner membrane diphosphatidylglycerol lipid marker cardiolipin. Together, our data indicate that PAGE4 specifically interacts with c-Jun and that, conformational dynamics may account for its observed pleiotropic functions. To our knowledge, this is the first report demonstrating crosstalk between a CTA and a proto-oncogene. Disrupting PAGE4/c-Jun interactions using small molecules may represent a novel therapeutic strategy for PCa.

Indexed as

Transcriptional Activation3' Untranslated RegionsAntigens, NeoplasmCell Line, TumorCyclin-Dependent Kinase Inhibitor p27Fluorescence Resonance Energy TransferGene Expression Regulation, NeoplasticHumansImmunohistochemistryMaleMicroRNAsMutationProstateProstatic NeoplasmsProtein BindingProtein Conformation3' Untranslated RegionsAntigens, NeoplasmCyclin-Dependent Kinase Inhibitor p27MAS1 protein, humanMicroRNAsMIR221, humanMIR222, humanPAGE4 protein, humanProto-Oncogene MasProto-Oncogene Proteins c-junbenign prostatic hyperplasiabovine serum albuminBPHBSACancer/Testis AntigenCDcircular dichroismc-JunDBDDimethyl sulfoxideDLSDMSODNA-binding domaindynamic light scatteringIntrinsically disordered proteinIPTGIsopropyl 1-thio-β-d-galactopyranosideNMRnuclear magnetic resonancePAGE4PBSPCPCaPEPhosphate Buffered SalinephosphatidylcholinephosphatidylethanolaminePIAPINPINspolyvinyl pyrollidoneproliferative inflammatory atrophyProstate Associated Gene 4prostate cancerProstate cancerprostatic intraepithelial neoplasiaprotein interaction networksPVPquantum yieldQYSDS-PAGESECsingle-molecule Förster resonance energy transfersize exclusion chromatographysmFRETSodium Dodecyl sulfate poly-acrylamide gel electrophoresisTCEP·HClTris(2-carboxyethyl)phosphine hydrochloride

Identifiers

PMID24263171
PMCPMC4086653
OpenAlexW2074000144

What OpenQuestion holds

Textmetadata
LicenceTDM
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.