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| - The role of microtubules (MTs) in steroid hormone-dependent human glucocorticoid receptor (hGR) activation/translocation is controversial. It was demonstrated recently that colchicine (COL) down-regulates hGR-driven genes in primary human hepatocytes by a mechanism involving inhibition of hGR translocation to the nucleus. To investigate whether inhibition of hGR translocation is the sole reason for its inactivation, we used human cervical carcinoma cells (HeLa) as a model. Herein we present evidence that perturbation of microtubules in HeLa cells leads to rapid time- and dose-dependent degradation of hGR protein. Degradation is proteasome mediated as revealed by its reversibility by proteasome inhibitor MG132. Moreover, degradation was observed for neither wt-hGR nor hGR mutants S226A and K419A in transiently transfected COS-1 cells. On the other hand, c-jun N-terminal kinase (JNK) seems not to be involved in the process because JNK inhibitor 1,9-Pyrazoloanthrone (SP600125) does not reverse hGR degrad
- The role of microtubules (MTs) in steroid hormone-dependent human glucocorticoid receptor (hGR) activation/translocation is controversial. It was demonstrated recently that colchicine (COL) down-regulates hGR-driven genes in primary human hepatocytes by a mechanism involving inhibition of hGR translocation to the nucleus. To investigate whether inhibition of hGR translocation is the sole reason for its inactivation, we used human cervical carcinoma cells (HeLa) as a model. Herein we present evidence that perturbation of microtubules in HeLa cells leads to rapid time- and dose-dependent degradation of hGR protein. Degradation is proteasome mediated as revealed by its reversibility by proteasome inhibitor MG132. Moreover, degradation was observed for neither wt-hGR nor hGR mutants S226A and K419A in transiently transfected COS-1 cells. On the other hand, c-jun N-terminal kinase (JNK) seems not to be involved in the process because JNK inhibitor 1,9-Pyrazoloanthrone (SP600125) does not reverse hGR degrad (en)
- Úloha mikrotubulů (MT) při aktivaci/translokaci lidského glukokortikoidního receptoru (hGR), která závisí na steroidních hormonech, je kontroverzní. Nedávno bylo prokázáno, že kolchicin (COL) snižuje expresi genů závislých na aktivitě hGR v primárních lidských hepatocytech mechanismem, který souvisí s inhibicí translokace hGR do jádra. Abychom zjistili, je-li inhibice translokace hGR jediným důvodem inaktivace tohoto receptoru, využili jsme buněčnou linii karcinomu lidského děložního čípku (HeLa) jako model. Zde předkládáme důkazy, že porušení mikrotubulů v HeLa buňkách vede k rychlé degradaci proteinu hGR v závislosti na čase a dávce. Degradace probíhá v proteasomu, což vyplývá z faktu, že ji lze zvrátit přídavkem inhibitoru proteasomu MG132. Navíc degradace nebyla pozorována ani v případě wt-hGR ani mutantů S226A a K419A, které byly transientně transfektovány do buněk COS-1. Na druhou stranu se ukazuje, že c-jun N-terminální kinasa (JNK) není do tohoto procesu zapojena, protože inhibitor JNK 1,9-pyr (cs)
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| Title
| - Disruption of microtubules leads to glucocorticoid receptor degradation in HeLa cell line
- Porušení sítě mikrotubulů v buněčné linii HeLa vede k degradaci glukokortikoidního receptoru (cs)
- Disruption of microtubules leads to glucocorticoid receptor degradation in HeLa cell line (en)
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| skos:prefLabel
| - Disruption of microtubules leads to glucocorticoid receptor degradation in HeLa cell line
- Porušení sítě mikrotubulů v buněčné linii HeLa vede k degradaci glukokortikoidního receptoru (cs)
- Disruption of microtubules leads to glucocorticoid receptor degradation in HeLa cell line (en)
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| skos:notation
| - RIV/61989592:15110/05:00001914!RIV06-MSM-15110___
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| http://linked.open.../vavai/riv/strany
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| http://linked.open...avai/riv/aktivita
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| http://linked.open...avai/riv/aktivity
| - P(GP303/04/P074), Z(MSM 151100003)
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| http://linked.open...iv/cisloPeriodika
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| http://linked.open...vai/riv/dodaniDat
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| http://linked.open...aciTvurceVysledku
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| http://linked.open.../riv/druhVysledku
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| http://linked.open...iv/duvernostUdaju
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| http://linked.open...titaPredkladatele
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| http://linked.open...dnocenehoVysledku
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| http://linked.open...ai/riv/idVysledku
| - RIV/61989592:15110/05:00001914
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| http://linked.open...riv/jazykVysledku
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| http://linked.open.../riv/klicovaSlova
| - Microtubules; glucocorticoid receptor; proteasome; degradation; translocation; c-jun N-terminal kinase; HeLa cells (en)
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| http://linked.open.../riv/klicoveSlovo
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| http://linked.open...odStatuVydavatele
| - US - Spojené státy americké
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| http://linked.open...ontrolniKodProRIV
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| http://linked.open...i/riv/nazevZdroje
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| http://linked.open...in/vavai/riv/obor
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| http://linked.open...ichTvurcuVysledku
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| http://linked.open...cetTvurcuVysledku
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| http://linked.open...vavai/riv/projekt
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| http://linked.open...UplatneniVysledku
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| http://linked.open...v/svazekPeriodika
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| http://linked.open...iv/tvurceVysledku
| - Dvořák, Zdeněk
- Ulrichová, Jitka
- Modrianský, Martin
- Maurel, Patrick
- Pascussi, Jean-Marc
- Vilarem, Marie-Jose
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| http://linked.open...n/vavai/riv/zamer
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| issn
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| number of pages
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| http://localhost/t...ganizacniJednotka
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| is http://linked.open...avai/riv/vysledek
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