"Dvo\u0159\u00E1k, Zden\u011Bk" . . . . "Modriansk\u00FD, Martin" . . "Ulrichov\u00E1, Jitka" . "Microtubules; glucocorticoid receptor; proteasome; degradation; translocation; c-jun N-terminal kinase; HeLa cells"@en . "0898-6568" . "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 . . "US - Spojen\u00E9 st\u00E1ty americk\u00E9" . . . "Disruption of microtubules leads to glucocorticoid receptor degradation in HeLa cell line" . . "\u00DAloha mikrotubul\u016F (MT) p\u0159i aktivaci/translokaci lidsk\u00E9ho glukokortikoidn\u00EDho receptoru (hGR), kter\u00E1 z\u00E1vis\u00ED na steroidn\u00EDch hormonech, je kontroverzn\u00ED. Ned\u00E1vno bylo prok\u00E1z\u00E1no, \u017Ee kolchicin (COL) sni\u017Euje expresi gen\u016F z\u00E1visl\u00FDch na aktivit\u011B hGR v prim\u00E1rn\u00EDch lidsk\u00FDch hepatocytech mechanismem, kter\u00FD souvis\u00ED s inhibic\u00ED translokace hGR do j\u00E1dra. Abychom zjistili, je-li inhibice translokace hGR jedin\u00FDm d\u016Fvodem inaktivace tohoto receptoru, vyu\u017Eili jsme bun\u011B\u010Dnou linii karcinomu lidsk\u00E9ho d\u011Blo\u017En\u00EDho \u010D\u00EDpku (HeLa) jako model. Zde p\u0159edkl\u00E1d\u00E1me d\u016Fkazy, \u017Ee poru\u0161en\u00ED mikrotubul\u016F v HeLa bu\u0148k\u00E1ch vede k rychl\u00E9 degradaci proteinu hGR v z\u00E1vislosti na \u010Dase a d\u00E1vce. Degradace prob\u00EDh\u00E1 v proteasomu, co\u017E vypl\u00FDv\u00E1 z faktu, \u017Ee ji lze zvr\u00E1tit p\u0159\u00EDdavkem inhibitoru proteasomu MG132. Nav\u00EDc degradace nebyla pozorov\u00E1na ani v p\u0159\u00EDpad\u011B wt-hGR ani mutant\u016F S226A a K419A, kter\u00E9 byly transientn\u011B transfektov\u00E1ny do bun\u011Bk COS-1. Na druhou stranu se ukazuje, \u017Ee c-jun N-termin\u00E1ln\u00ED kinasa (JNK) nen\u00ED do tohoto procesu zapojena, proto\u017Ee inhibitor JNK 1,9-pyr"@cs . "Cellular Signalling" . . "Vilarem, Marie-Jose" . "Pascussi, Jean-Marc" . "17" . "2" . "15110" . "6"^^ . "RIV/61989592:15110/05:00001914!RIV06-MSM-15110___" . "RIV/61989592:15110/05:00001914" . "Disruption of microtubules leads to glucocorticoid receptor degradation in HeLa cell line"@en . . . "Maurel, Patrick" . . . "10"^^ . "187-196" . "3"^^ . . "Disruption of microtubules leads to glucocorticoid receptor degradation in HeLa cell line" . . . "[275CD2E87319]" . . "518296" . . "P(GP303/04/P074), Z(MSM 151100003)" . . "Poru\u0161en\u00ED s\u00EDt\u011B mikrotubul\u016F v bun\u011B\u010Dn\u00E9 linii HeLa vede k degradaci glukokortikoidn\u00EDho receptoru"@cs . "Poru\u0161en\u00ED s\u00EDt\u011B mikrotubul\u016F v bun\u011B\u010Dn\u00E9 linii HeLa vede k degradaci glukokortikoidn\u00EDho receptoru"@cs . . . . "Disruption of microtubules leads to glucocorticoid receptor degradation in HeLa cell line"@en . "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" . .