Evidence map›Paper›PMID 24559171›Full record

ArticleBiochemistry2014

Cancer/testis antigen PAGE4, a regulator of c-Jun transactivation, is phosphorylated by homeodomain-interacting protein kinase 1, a component of the stress-response pathway.

Steven M Mooney, Ruoyi Qiu, John J Kim, Elizabeth J Sacho, Krithika Rajagopalan, Dorhyun Johng, Takumi Shiraishi, Prakash Kulkarni, Keith R Weninger

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biochemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
6.4field-weighted citation impact, top 4% 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

26 citing papers in PubMed, 46 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

9 authors at 4 institutions in 1 country.

Steven M MooneyThe James Buchanan Brady Urological Institute and Department of Urology, ‡Oncology, §Cellular and Molecular Medicine, and ∥Department of Biomedical Engineering, Whiting School of Engineering, The Johns Hopkins University School of Medicine , 733 North Broadway, Baltimore, Maryland 21205, United States.
Ruoyi Qiu
John J Kim
Elizabeth J Sacho
Krithika Rajagopalan
Dorhyun Johng
Takumi Shiraishi
Prakash Kulkarni
Keith R Weninger
North Carolina State University · USUniversity of California, Berkeley · USInstitute for Bioscience and Biotechnology ResearchJohns Hopkins University · US

Funding

PAGE4 as a Novel Target for Prostate Cancer PreventionR21CA181730 · NCI · UNIV OF MARYLAND, COLLEGE PARK · PI KULKARNI, PRAKASH, ORBAN, JOHN · 2014 to 2015
$364k
NCI NIH HHS CA181730NCI NIH HHS R21 CA181730
6 · The paper itself

Abstract

Prostate-associated gene 4 (PAGE4) is a cancer/testis antigen that is typically restricted to the testicular germ cells but is aberrantly expressed in cancer. Furthermore, PAGE4 is developmentally regulated with dynamic expression patterns in the developing prostate and is also a stress-response protein that is upregulated in response to cellular stress. PAGE4 interacts with c-Jun, which is activated by the stress-response kinase JNK1, and plays an important role in the development and pathology of the prostate gland. Here, we have identified homeodomain-interacting protein kinase 1 (HIPK1), also a component of the stress-response pathway, as a kinase that phosphorylates PAGE4 at T51. We show that phosphorylation of PAGE4 is critical for its transcriptional activity since mutating this T residue abolishes its ability to potentiate c-Jun transactivation. In vitro single molecule FRET indicates phosphorylation results in compaction of (still) intrinsically disordered PAGE4. Interestingly, however, while our previous observations indicated that the wild-type nonphosphorylated PAGE4 protein interacted with c-Jun [Rajagopalan , K. et al. ( 2014 ) Biochim, Biophys. Acta 1842 , 154 -163], here we show that phosphorylation of PAGE4 weakens its interaction with c-Jun in vitro. These data suggest that phosphorylation induces conformational changes in natively disordered PAGE4 resulting in its decreased affinity for c-Jun to promote interaction of c-Jun with another, unidentified, partner. Alternatively, phosphorylated PAGE4 may induce transcription of a novel partner, which then potentiates c-Jun transactivation. Regardless, the present results clearly implicate PAGE4 as a component of the stress-response pathway and uncover a novel link between components of this pathway and prostatic development and disease.

Indexed as

Transcriptional ActivationAmino Acid MotifsAntigens, NeoplasmCell Line, TumorHumansMalePhosphorylationProstatic NeoplasmsProtein BindingProtein Serine-Threonine KinasesProto-Oncogene Proteins c-junSignal TransductionStress, PhysiologicalTestisAntigens, NeoplasmHIPK1 protein, humanPAGE4 protein, humanProtein Serine-Threonine KinasesProto-Oncogene Proteins c-jun

Identifiers

PMID24559171
PMCPMC4198062
OpenAlexW2330741207

What OpenQuestion holds

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Read underepoch 390

Registered trials

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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.