Inhibition of glycogen synthase kinase‐3β promotes nuclear export of the androgen receptor through a CRM1‐dependent mechanism in prostate cancer cell lines
Identifieur interne : 000019 ( Allemagne/Analysis ); précédent : 000018; suivant : 000020Inhibition of glycogen synthase kinase‐3β promotes nuclear export of the androgen receptor through a CRM1‐dependent mechanism in prostate cancer cell lines
Auteurs : Stefanie V. Schütz [Allemagne] ; Marcus V. Cronauer [Allemagne] ; Ludwig Rinnab [Allemagne]Source :
- Journal of Cellular Biochemistry [ 0730-2312 ] ; 2010-04-15.
English descriptors
- KwdEn :
Abstract
The androgen receptor (AR) is a ligand‐dependent transcription factor belonging to the steroid hormone receptor superfamily. Under normal conditions, in the absence of a ligand, the AR is localized to the cytoplasm and is actively transported into the nucleus upon binding of androgens. In advanced prostate cancer (PCa) cell lines, an increased sensitivity to dihydrotestosterone (DHT), enabling the cells to proliferate under sub‐physiological levels of androgens, has been associated with increased stability and nuclear localization of the AR. There is experimental evidence that the glycogen synthase kinase‐3β (GSK‐3β), a multifunctional serine/threonine kinase is involved in estrogen and AR stability. As demonstrated in the following study by immunoprecipitation analysis, GSK‐3β binds to the AR forming complexes in the cytoplasm and in the nucleus. Furthermore, inhibition of GSK‐3β activity by pharmacological inhibitors like the maleimide SB216761, the chloromethyl‐thienyl‐ketone GSK‐3 inhibitor VI or the aminopyrazol GSK‐3 inhibitor XIII in cells grown in the presence of DHT triggered a rapid nuclear export of endogenous AR as well as of green fluorescent AR‐EosFP. The nuclear export of AR following GSK‐3β inhibition could be blocked by leptomycin B suggesting a CRM1‐dependent export mechanism. This assumption is supported by the localization of a putative CRM1 binding site at the C‐terminus of the AR protein. The results suggest that GSK‐3β is an important element not only in AR stability but also significantly alters nuclear translocation of the AR, thereby modulating the androgenic response of human PCa cells. J. Cell. Biochem. 109: 1192–1200, 2010. © 2010 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/jcb.22500
Affiliations:
Links toward previous steps (curation, corpus...)
- to stream Main, to step Corpus: 000860
- to stream Main, to step Curation: 000854
- to stream Main, to step Exploration: 000134
- to stream Allemagne, to step Extraction: 000019
Links to Exploration step
ISTEX:3AAF6A14E8AFCC22B266CE831F2BDB0497AF2D4ALe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Inhibition of glycogen synthase kinase‐3β promotes nuclear export of the androgen receptor through a CRM1‐dependent mechanism in prostate cancer cell lines</title><author><name sortKey="Schutz, Stefanie V" sort="Schutz, Stefanie V" uniqKey="Schutz S" first="Stefanie V." last="Schütz">Stefanie V. Schütz</name></author><author><name sortKey="Cronauer, Marcus V" sort="Cronauer, Marcus V" uniqKey="Cronauer M" first="Marcus V." last="Cronauer">Marcus V. Cronauer</name></author><author><name sortKey="Rinnab, Ludwig" sort="Rinnab, Ludwig" uniqKey="Rinnab L" first="Ludwig" last="Rinnab">Ludwig Rinnab</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:3AAF6A14E8AFCC22B266CE831F2BDB0497AF2D4A</idno><date when="2010" year="2010">2010</date><idno type="doi">10.1002/jcb.22500</idno><idno type="url">https://api.istex.fr/document/3AAF6A14E8AFCC22B266CE831F2BDB0497AF2D4A/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">000860</idno><idno type="wicri:Area/Main/Curation">000854</idno><idno type="wicri:Area/Main/Exploration">000134</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Exploration">000134</idno><idno type="wicri:Area/Allemagne/Extraction">000019</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Inhibition of glycogen synthase kinase‐3β promotes nuclear export of the androgen receptor through a CRM1‐dependent mechanism in prostate cancer cell lines</title><author><name sortKey="Schutz, Stefanie V" sort="Schutz, Stefanie V" uniqKey="Schutz S" first="Stefanie V." last="Schütz">Stefanie V. Schütz</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of General Zoology and Endocrinology, Ulm University, 89069 Ulm</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Ulm</settlement></placeName></affiliation><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Urology, Ulm University, 89069 Ulm</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Ulm</settlement></placeName></affiliation></author><author><name sortKey="Cronauer, Marcus V" sort="Cronauer, Marcus V" uniqKey="Cronauer M" first="Marcus V." last="Cronauer">Marcus V. Cronauer</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Institute of General Zoology and Endocrinology, Ulm University, 89069 Ulm</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Ulm</settlement></placeName></affiliation></author><author><name sortKey="Rinnab, Ludwig" sort="Rinnab, Ludwig" uniqKey="Rinnab L" first="Ludwig" last="Rinnab">Ludwig Rinnab</name><affiliation wicri:level="3"><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Urology, Ulm University, 89069 Ulm</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Ulm</settlement></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Journal of Cellular Biochemistry</title><title level="j" type="abbrev">J. Cell. Biochem.</title><idno type="ISSN">0730-2312</idno><idno type="eISSN">1097-4644</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2010-04-15">2010-04-15</date><biblScope unit="volume">109</biblScope><biblScope unit="issue">6</biblScope><biblScope unit="page" from="1192">1192</biblScope><biblScope unit="page" to="1200">1200</biblScope></imprint><idno type="ISSN">0730-2312</idno></series><idno type="istex">3AAF6A14E8AFCC22B266CE831F2BDB0497AF2D4A</idno><idno type="DOI">10.1002/jcb.22500</idno><idno type="ArticleID">JCB22500</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0730-2312</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>CRM1</term><term>GSK‐3β</term><term>androgen receptor</term><term>nuclear export</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The androgen receptor (AR) is a ligand‐dependent transcription factor belonging to the steroid hormone receptor superfamily. Under normal conditions, in the absence of a ligand, the AR is localized to the cytoplasm and is actively transported into the nucleus upon binding of androgens. In advanced prostate cancer (PCa) cell lines, an increased sensitivity to dihydrotestosterone (DHT), enabling the cells to proliferate under sub‐physiological levels of androgens, has been associated with increased stability and nuclear localization of the AR. There is experimental evidence that the glycogen synthase kinase‐3β (GSK‐3β), a multifunctional serine/threonine kinase is involved in estrogen and AR stability. As demonstrated in the following study by immunoprecipitation analysis, GSK‐3β binds to the AR forming complexes in the cytoplasm and in the nucleus. Furthermore, inhibition of GSK‐3β activity by pharmacological inhibitors like the maleimide SB216761, the chloromethyl‐thienyl‐ketone GSK‐3 inhibitor VI or the aminopyrazol GSK‐3 inhibitor XIII in cells grown in the presence of DHT triggered a rapid nuclear export of endogenous AR as well as of green fluorescent AR‐EosFP. The nuclear export of AR following GSK‐3β inhibition could be blocked by leptomycin B suggesting a CRM1‐dependent export mechanism. This assumption is supported by the localization of a putative CRM1 binding site at the C‐terminus of the AR protein. The results suggest that GSK‐3β is an important element not only in AR stability but also significantly alters nuclear translocation of the AR, thereby modulating the androgenic response of human PCa cells. J. Cell. Biochem. 109: 1192–1200, 2010. © 2010 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>Bade-Wurtemberg</li><li>District de Tübingen</li></region><settlement><li>Ulm</li></settlement></list><tree><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Schutz, Stefanie V" sort="Schutz, Stefanie V" uniqKey="Schutz S" first="Stefanie V." last="Schütz">Stefanie V. Schütz</name></region><name sortKey="Cronauer, Marcus V" sort="Cronauer, Marcus V" uniqKey="Cronauer M" first="Marcus V." last="Cronauer">Marcus V. Cronauer</name><name sortKey="Rinnab, Ludwig" sort="Rinnab, Ludwig" uniqKey="Rinnab L" first="Ludwig" last="Rinnab">Ludwig Rinnab</name><name sortKey="Schutz, Stefanie V" sort="Schutz, Stefanie V" uniqKey="Schutz S" first="Stefanie V." last="Schütz">Stefanie V. Schütz</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Musique/explor/SchutzV1/Data/Allemagne/Analysis
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000019 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Allemagne/Analysis/biblio.hfd -nk 000019 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Musique
|area= SchutzV1
|flux= Allemagne
|étape= Analysis
|type= RBID
|clé= ISTEX:3AAF6A14E8AFCC22B266CE831F2BDB0497AF2D4A
|texte= Inhibition of glycogen synthase kinase‐3β promotes nuclear export of the androgen receptor through a CRM1‐dependent mechanism in prostate cancer cell lines
}}
| This area was generated with Dilib version V0.6.38. |  |