Nuclear compartmentalization of N-CoR and its interactions with steroid receptors.
The repression mechanisms by the nuclear receptor corepressor (N-CoR) of steroid hormone receptor (SHR)-mediated transactivation were examined. Yellow fluorescent protein (YFP)-N-CoR was distributed as intranuclear discrete dots, while coexpression of androgen receptor (AR), glucocorticoid receptor alpha, and estrogen receptor alpha ligand-dependently triggered redistribution of YFP-N-CoR. In fluorescence recovery after photobleaching ... analysis, mobility of the N-CoR was reduced by 5alpha-dihydrotestosterone (DHT)-bound AR. The middle region of N-CoR mostly contributed to the interaction with agonist-bound SHRs and the suppression of their transactivation function. N-CoR impaired the DHT-induced N-C interaction of AR, and the impaired interaction was dose-dependently recovered by coexpression of SRC-1 and CBP. N-CoR also impaired the intranuclear complete (distinct) focus formation of SHRs. Coexpression of SRC-1 or CBP released YFP-N-CoR or endogenous N-CoR from incomplete foci and simultaneously recovered complete foci of AR-green fluorescent protein. These results indicate that the relative ratio of coactivators and corepressors determines the conformational equilibrium between transcriptionally active and inactive SHRs in the presence of agonists. The intranuclear foci formed by agonist-bound SHRs were completely destroyed by actinomycin D and alpha-amanitin, indicating that the focus formation does not precede the transcriptional activation. The focus formation may reflect the accumulation of SHR/coactivator complexes released from the transcriptionally active sites and thus be a mirror of transcriptionally active complex formation.
Mesh Terms:
3T3-L1 Cells, Animals, COS Cells, CREB-Binding Protein, Cell Compartmentation, Cell Line, Tumor, Cell Nucleus Structures, Cells, Cultured, Cercopithecus aethiops, Dihydrotestosterone, Green Fluorescent Proteins, Histone Acetyltransferases, Humans, Ligands, Mice, Mutant Proteins, NIH 3T3 Cells, Nuclear Proteins, Nuclear Receptor Co-Repressor 1, Nuclear Receptor Coactivator 1, Protein Binding, Protein Transport, RNA Splicing, Receptors, Androgen, Receptors, Steroid, Repressor Proteins, Transcription Factors, Transcriptional Activation
3T3-L1 Cells, Animals, COS Cells, CREB-Binding Protein, Cell Compartmentation, Cell Line, Tumor, Cell Nucleus Structures, Cells, Cultured, Cercopithecus aethiops, Dihydrotestosterone, Green Fluorescent Proteins, Histone Acetyltransferases, Humans, Ligands, Mice, Mutant Proteins, NIH 3T3 Cells, Nuclear Proteins, Nuclear Receptor Co-Repressor 1, Nuclear Receptor Coactivator 1, Protein Binding, Protein Transport, RNA Splicing, Receptors, Androgen, Receptors, Steroid, Repressor Proteins, Transcription Factors, Transcriptional Activation
Mol. Cell. Biol.
Date: Sep. 01, 2006
PubMed ID: 16914745
View in: Pubmed Google Scholar
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