A Serine/Threonine-rich Motif Is One of Three Nuclear Localization Signals That Determine Unidirectional Transport of the Mineralocorticoid Receptor to the Nucleus
Autor: | Amanda Carrigan, Laura Visentin, Ella Atlas, Gregory C. Addicks, Yanouchka Rouleau, Allison Edgecombe, Claudia Lamprecht, Yvonne A. Lefebvre, Robert J. G. Haché, Rhian F. Walther |
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Rok vydání: | 2005 |
Předmět: |
Threonine
Cytoplasm Time Factors Amino Acid Motifs Blotting Western Green Fluorescent Proteins Molecular Sequence Data Nuclear Localization Signals Active Transport Cell Nucleus Biology Ligands Transfection Biochemistry Receptors Glucocorticoid Serine Animals Humans Nuclear Matrix Amino Acid Sequence Phosphorylation Fluorescent Antibody Technique Indirect Nuclear export signal Molecular Biology Nuclear receptor co-repressor 1 Glutathione Transferase Cell Nucleus Biological Transport Cell Biology Protein Structure Tertiary Cell biology Nuclear receptor coactivator 1 Receptors Mineralocorticoid Nuclear receptor COS Cells Nuclear receptor coactivator 3 Nuclear receptor coactivator 2 Steroids Nuclear transport Nuclear localization sequence Fluorescence Recovery After Photobleaching HeLa Cells Plasmids |
Zdroj: | Journal of Biological Chemistry. 280:17549-17561 |
ISSN: | 0021-9258 |
Popis: | The mineralocorticoid receptor (MR) is a tightly regulated nuclear hormone receptor that selectively transmits corticosteroid signals. Steroid treatment transforms MR from a transcriptionally inert state, in which it is distributed equally between the nucleus and cytoplasm, to an active completely nuclear transcription factor. We report here that MR is an atypical nuclear hormone receptor that moves unidirectionally from the cytoplasm to the nucleus. We show that nuclear import of MR is controlled through three nuclear localization signals (NLSs) of distinct types. Nuclear localization of naive MR was mediated primarily through a novel serine/threonine-rich NLS (NL0) in the receptor N terminus. Specific amino acid substitutions that mimicked phosphorylation selectively enhanced or repressed NL0 activity, highlighting the potential for active regulation of this new type of NLS. The second NLS (NL2) within the ligand-binding domain also lacks a recognizable basic motif. Nuclear transfer through this signal was strictly dependent on steroid agonist, but was independent of the interaction of MR with coactivator proteins. The third MR NLS (NL1) is a bipartite basic motif localized to the C terminus of the MR DNA-binding domain with properties distinct from those of NL1 of the closely related glucocorticoid receptor. NL1 acted in concert with NL0 and NL2 to stimulate nuclear uptake of the agonist-treated receptor, but also directed the complete nuclear localization of MR in response to treatment with steroid antagonist. These results present MR as a nuclear hormone receptor whose unidirectional transfer to the nucleus may be regulated through multiple pathways. |
Databáze: | OpenAIRE |
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