RRC ID 42732
著者 Wu Y, Kawate H, Ohnaka K, Nawata H, Takayanagi R.
タイトル Nuclear compartmentalization of N-CoR and its interactions with steroid receptors.
ジャーナル Mol Cell Biol
Abstract 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.
巻・号 26(17)
ページ 6633-55
公開日 2006-9-1
DOI 10.1128/MCB.01534-05
PII 26/17/6633
PMID 16914745
PMC PMC1592818
MeSH 3T3-L1 Cells Animals COS Cells CREB-Binding Protein / metabolism Cell Compartmentation* Cell Line, Tumor Cell Nucleus Structures / drug effects Cell Nucleus Structures / metabolism* Cells, Cultured Chlorocebus aethiops Dihydrotestosterone / pharmacology Green Fluorescent Proteins / metabolism Histone Acetyltransferases Humans Ligands Mice Mutant Proteins / metabolism NIH 3T3 Cells Nuclear Proteins / metabolism* Nuclear Receptor Co-Repressor 1 Nuclear Receptor Coactivator 1 Protein Binding / drug effects Protein Transport / drug effects RNA Splicing / drug effects Receptors, Androgen / metabolism Receptors, Steroid / agonists Receptors, Steroid / metabolism* Repressor Proteins / metabolism* Transcription Factors / metabolism Transcriptional Activation / drug effects
IF 3.611
引用数 29
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 COS-7(RCB0539)