TY - JOUR
T1 - Regulation of glucocorticoid receptor activity by 14-3-3-dependent intracellular relocalization of the corepressor RIP140
AU - Zilliacus, Johanna
AU - Holter, Elin
AU - Wakui, Hideki
AU - Tazawa, Hiroshi
AU - Treuter, Eckardt
AU - Gustafsson, Jan Åke
PY - 2001/5/1
Y1 - 2001/5/1
N2 - Proteins belonging to the 14-3-3 family interact with various regulatory proteins involved in cellular signaling, cell cycle regulation, or apoptosis. 14-3-3 proteins have been suggested to act by regulating the cytoplasmic/nuclear localization of their target proteins or by acting as molecular scaffolds or chaperones. We have previously shown that overexpression of 14-3-3 enhances the transcriptional activity of the glucocorticoid receptor (GR), which is a member of the nuclear receptor family. In this study, we show that 14-3-3 interacts with the nuclear receptor corepressor RIP140. In transfection assays, RIP140 antagonizes 14-3-3-enhanced GR transactivation. Using colocalization studies we demonstrate that 14-3-3 can export RIP140 out of the nucleus and, interestingly, can also change its intranuclear localization. Moreover, we also observed that 14-3-3 can bind various other nuclear receptors and cofactors. In summary, our findings suggest that 14-3-3-mediated intracellular relocalization of the GR corepressor RIP140 might be a novel mechanism to enhance glucocorticoid responsiveness of target genes. They furthermore indicate a more general role for 14-3-3 protein by influencing the nuclear availability of nuclear receptor-associated cofactors.
AB - Proteins belonging to the 14-3-3 family interact with various regulatory proteins involved in cellular signaling, cell cycle regulation, or apoptosis. 14-3-3 proteins have been suggested to act by regulating the cytoplasmic/nuclear localization of their target proteins or by acting as molecular scaffolds or chaperones. We have previously shown that overexpression of 14-3-3 enhances the transcriptional activity of the glucocorticoid receptor (GR), which is a member of the nuclear receptor family. In this study, we show that 14-3-3 interacts with the nuclear receptor corepressor RIP140. In transfection assays, RIP140 antagonizes 14-3-3-enhanced GR transactivation. Using colocalization studies we demonstrate that 14-3-3 can export RIP140 out of the nucleus and, interestingly, can also change its intranuclear localization. Moreover, we also observed that 14-3-3 can bind various other nuclear receptors and cofactors. In summary, our findings suggest that 14-3-3-mediated intracellular relocalization of the GR corepressor RIP140 might be a novel mechanism to enhance glucocorticoid responsiveness of target genes. They furthermore indicate a more general role for 14-3-3 protein by influencing the nuclear availability of nuclear receptor-associated cofactors.
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U2 - 10.1210/me.15.4.501
DO - 10.1210/me.15.4.501
M3 - Article
C2 - 11266503
AN - SCOPUS:0035064047
VL - 15
SP - 501
EP - 511
JO - Molecular Endocrinology
JF - Molecular Endocrinology
SN - 0888-8809
IS - 4
ER -