論文 - 詳細
| RRC ID | 1485 |
|---|---|
| 著者 | Shimizu N, Ouchida R, Yoshikawa N, Hisada T, Watanabe H, Okamoto K, Kusuhara M, Handa H, Morimoto C, Tanaka H. |
| タイトル | HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor without involving 7SK RNA and positive transcription elongation factor b. |
| ジャーナル | Proc Natl Acad Sci U S A |
| Abstract |
The HEXIM1 protein has been shown to form a protein-RNA complex composed of 7SK small nuclear RNA and positive transcription elongation factor b (P-TEFb), which is composed of cyclin-dependent kinase 9 (CDK9) and cyclin T1, and to inhibit the kinase activity of CDK9, thereby suppressing RNA polymerase II-dependent transcriptional elongation. Here, we biochemically demonstrate that HEXIM1 forms a distinct complex with glucocorticoid receptor (GR) without RNA, CDK9, or cyclin T1. HEXIM1, through its arginine-rich nuclear localization signal, directly associates with the ligand-binding domain of GR. Introduction of HEXIM1 short interfering RNA and adenovirus-mediated exogenous expression of HEXIM1 positively and negatively modulated glucocorticoid-responsive gene activation, respectively. In the nucleus, HEXIM1 was shown to localize in a distinct compartment from that of the p160 coactivator transcriptional intermediary factor 2. Overexpression of HEXIM1 decreased ligand-dependent association between GR and transcriptional intermediary factor 2. Antisense-mediated disruption of 7SK blunted the negative effect of HEXIM1 on arylhydrocarbon receptor-dependent transcription but not on GR-mediated one, indicating that a class of transcription factors are direct targets of HEXIM1. These results indicate that HEXIM1 has dual roles in transcriptional regulation: inhibition of transcriptional elongation dependent on 7SK RNA and positive transcription elongation factor b and interference with the sequence-specific transcription factor GR via a direct protein-protein interaction. Moreover, the fact that the central nuclear localization signal of HEXIM1 is essential for both of these actions may argue the crosstalk of these functions. |
| 巻・号 | 102(24) |
| ページ | 8555-60 |
| 公開日 | 2005-6-14 |
| DOI | 10.1073/pnas.0409863102 |
| PII | 0409863102 |
| PMID | 15941832 |
| PMC | PMC1150813 |
| MeSH | Animals COS Cells Chlorocebus aethiops Fluorescent Antibody Technique, Indirect Gene Expression Regulation* Glutathione Transferase HeLa Cells Humans Immunoprecipitation Luciferases Mass Spectrometry Multiprotein Complexes / metabolism* Nuclear Receptor Coactivator 2 Oligonucleotide Array Sequence Analysis Protein Binding Protein Structure, Tertiary RNA, Small Interfering / genetics RNA-Binding Proteins / metabolism* Receptors, Glucocorticoid / metabolism* Reverse Transcriptase Polymerase Chain Reaction Transcription Factors / metabolism Transcriptional Activation Transfection |
| IF | 9.412 |
| 引用数 | 34 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | HeLa(RCB0007) COS-7(RCB0539) Hep G2 |