Disruption of microtubules leads to glucocorticoid receptor degradation in HeLa cell line.

Abstract:

: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 degradation. Similarly, another hGR functional antagonist, nuclear factor kappa beta (NFkappaB), did not play any role in the degradation process.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Dvorák Z,Modrianský M,Ulrichová J,Maurel P,Vilarem MJ,Pascussi JM

doi

10.1016/j.cellsig.2004.06.010

subject

Has Abstract

pub_date

2005-02-01 00:00:00

pages

187-96

issue

2

eissn

0898-6568

issn

1873-3913

pii

S0898-6568(04)00139-1

journal_volume

17

pub_type

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