An active nuclear retention signal in the glucocorticoid receptor functions as a strong inducer of transcriptional activation
Autor: | Houssein Abdou Salem, Yvonne A. Lefebvre, Dongmei Wu, Robert J.G. Haché, Amanda Carrigan, Rhian F. Walther, Ella Atlas |
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Rok vydání: | 2007 |
Předmět: |
Transcriptional Activation
Molecular Sequence Data Active Transport Cell Nucleus Importin Biology Biochemistry Glucocorticoid receptor Receptors Glucocorticoid Chlorocebus aethiops medicine Animals Amino Acid Sequence Amino Acids Nuclear export signal Promoter Regions Genetic Molecular Biology Karyopherin chemistry.chemical_classification Cell Biology Cell biology Rats Cell nucleus medicine.anatomical_structure chemistry COS Cells Nuclear receptor coactivator 2 Nuclear transport Nuclear localization sequence Signal Transduction |
Zdroj: | The Journal of biological chemistry. 282(15) |
ISSN: | 0021-9258 |
Popis: | The glucocorticoid receptor (GR) cycles between a naive chaperone-complexed form in the cytoplasm and a transcriptionally active steroid-bound nuclear form. Nuclear import of GR occurs rapidly and is mediated through the importin alpha/beta karyopherin import pathway. By contrast, nuclear export of GR occurs only slowly under most conditions, despite a dependence on active signaling. In this study we have defined a nuclear retention signal (NRS) in the hinge region of GR that actively opposes the nuclear export of GR as well as the nuclear export mediated through an ectopic CRM1-dependent nuclear export signal (NES). The GR NRS overlaps closely with the basic NL1 nuclear localization signal (NLS) but can be distinguished from NL1 by targeted mutagenesis. Substitution of the classical NLS from SV40 T antigen for the GR NL1 results in a receptor in which nuclear export is accelerated. Remarkably, although the SV40-modified GR remains predominantly nuclear in the presence of steroid and is recruited to transcriptional regulatory regions indistinguishably from wild-type GR, the substitution dramatically weakens the ability of GR to activate transcription of a mouse mammary tumor virus reporter gene. These results suggest that active nuclear retention of GR plays an integral role in glucocorticoid signaling. |
Databáze: | OpenAIRE |
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