| RRC ID |
43331
|
| 著者 |
Yoshikawa N, Shimizu N, Sano M, Ohnuma K, Iwata S, Hosono O, Fukuda K, Morimoto C, Tanaka H.
|
| タイトル |
Role of the hinge region of glucocorticoid receptor for HEXIM1-mediated transcriptional repression.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
We previously reported that HEXIM1 (hexamethylene bisacetamide-inducible protein 1), which suppresses transcription elongation via sequestration of positive transcription elongation factor b (P-TEFb) using 7SK RNA as a scaffold, directly associates with glucocorticoid receptor (GR) to suppress glucocorticoid-inducible gene activation. Here, we revealed that the hinge region of GR is essential for its interaction with HEXIM1, and that oxosteroid receptors including GR show sequence homology in their hinge region and interact with HEXIM1, whereas the other members of nuclear receptors do not. We also showed that HEXIM1 suppresses GR-mediated transcription in two ways: sequestration of P-TEFb by HEXIM1 and direct interaction between GR and HEXIM1. In contrast, peroxisome proliferator-activated receptor gamma-dependent gene expression is negatively modulated by HEXIM1 solely via sequestration of P-TEFb. We, therefore, conclude that HEXIM1 may act as a gene-selective transcriptional regulator via direct interaction with certain transcriptional regulators including GR and contribute to fine-tuning of, for example, glucocorticoid-mediated biological responses.
|
| 巻・号 |
371(1)
|
| ページ |
44-9
|
| 公開日 |
2008-6-20
|
| DOI |
10.1016/j.bbrc.2008.03.155
|
| PII |
S0006-291X(08)00634-7
|
| PMID |
18407829
|
| MeSH |
Amino Acid Sequence
Animals
Down-Regulation
Gene Expression Regulation*
Humans
Ketosteroids / metabolism
Molecular Sequence Data
PPAR gamma / metabolism
Positive Transcriptional Elongation Factor B / metabolism
Protein Interaction Mapping
Protein Structure, Tertiary
RNA-Binding Proteins / chemistry
RNA-Binding Proteins / metabolism*
Receptors, Glucocorticoid / chemistry
Receptors, Glucocorticoid / genetics
Receptors, Glucocorticoid / metabolism*
Sequence Homology, Amino Acid
Transcription Factors
Transcription, Genetic*
Transcriptional Activation
|
| IF |
2.985
|
| 引用数 |
8
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539) |
