Evidence map›Paper›PMID 19622840›Full record

ArticleThe Journal of biological chemistry2009

Androgen receptor phosphorylation and activity are regulated by an association with protein phosphatase 1.

Shaoyong Chen, Cristina T Kesler, Bryce M Paschal, Steven P Balk

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.8field-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

44 citing papers in PubMed, 81 citations in OpenAlex.

  1. Review
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  8. Pathogenic mechanisms underlying spinocerebellar ataxia type 1.Cellular and molecular life sciences : CMLS · 2020
    Review
  9. Review
  10. Molecular Mechanisms and Therapeutics for SBMA/Kennedy's Disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2019
    Review
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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

4 authors at 2 institutions in 1 country.

Shaoyong ChenCancer Biology Program, Hematology-Oncology Division, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. schen@bidmc.harvard.edu
Cristina T Kesler
Bryce M Paschal
Steven P Balk
Beth Israel Deaconess Medical Center · USUniversity of Virginia Health System · US

Funding

Tumor and Circulating Markers as Links Between Obesity and Lethal Prostate CanceP50CA090381 · NCI · DANA-FARBER CANCER INSTITUTE · PI BALK, STEVEN P. · 2002 to 2017
$36.2M
Targeting AR-NCoR Interaction in Prostate CancerR01CA111803 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI BALK, STEVEN P. · 2007 to 2011
$1.6M
Androgen Receptor Regulation by PhosphorylationK99CA135592 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CHEN, SHAOYONG · 2008 to 2009
$195k
NCI NIH HHS K99 CA135592NCI NIH HHS K99CA135592NCI NIH HHS P01CA10406NCI NIH HHS P50 CA090381NCI NIH HHS P50 CA90381NCI NIH HHS R01 CA111803NCI NIH HHS R01CA111803
6 · The paper itself

Abstract

Androgen receptor (AR) is phosphorylated at multiple sites in response to ligand binding, but the functional consequences and mechanisms regulating AR phosphorylation remain to be established. We observed initially that okadaic acid, an inhibitor of the major PPP family serine/threonine phosphatases PP2A and protein phosphatase 1 (PP1), had cell type-dependent effects on AR expression. More specific inhibitors of PP2A (fostriecin) and PP1 (tautomycin and siRNA against the PP1alpha catalytic subunit) demonstrated that PP1 and protein phosphatase 2A had opposite effects on AR protein and transcriptional activity. PP1 inhibition enhanced proteasome-mediated AR degradation, while PP1alpha overexpression increased AR expression and markedly enhanced AR transcriptional activity. Coprecipitation experiments demonstrated an AR-PP1 interaction, while immunofluorescence and nuclear-cytoplasmic fractionation showed androgen-stimulated nuclear translocation of both AR and PP1 in prostate cancer cells. Studies with phosphospecific AR antibodies showed that PP1 inhibition dramatically increased phosphorylation of Ser-650, a site in the AR hinge region shown to mediate nuclear export. Significantly, PP1 inhibition caused a marked decrease in nuclear localization of the wild-type AR, but did not alter total or nuclear levels of a S650A mutant AR. These findings reveal a critical role of PP1 in regulating AR protein stability and nuclear localization through dephosphorylation of Ser-650. Moreover, AR may function as a PP1 regulatory subunit and mediate PP1 recruitment to chromatin, where it can modulate transcription and splicing.

Indexed as

Active Transport, Cell NucleusCell LineCell NucleusChromatinEnzyme InhibitorsGene Expression RegulationHumansPhosphorylationProteasome Endopeptidase ComplexProteasome InhibitorsProtein Phosphatase 1Protein Phosphatase 2Receptors, AndrogenTranscription, GeneticChromatinEnzyme InhibitorsPPP2CA protein, humanProteasome Endopeptidase ComplexProteasome InhibitorsProtein Phosphatase 1Protein Phosphatase 2Receptors, Androgen

Identifiers

PMID19622840
PMCPMC2757959
OpenAlexW2014675339

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.