Molecular mechanism for the potentiation of the transcriptional activity of human liver receptor homolog 1 by steroid receptor coactivator-1
文献类型：期刊论文
| 作者 | Xu, PL; Liu, YQ; Shan, SF; Kong, YY; Zhou, Q; Li, M; Ding, JP; Xie, YH; Wang, Y |
| 刊名 | MOLECULAR ENDOCRINOLOGY
 |
| 出版日期 | 2004 |
| 卷号 | 18期号:8页码:1887-1905 |
| 通讯作者 | Ding, JP (reprint author), Chinese Acad Sci, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.,jpding@sibs.ac.cn ; yhxie@sibs.ac.cn ; wangy@sibs.ac.cn |
| 英文摘要 | The liver receptor homolog 1 (LRH-1) belongs to the Fushi tarazu factor 1 nuclear receptor subfamily, and its biological functions are just being unveiled. The molecular mechanism for the transcriptional regulation by LRH-1 is not clear yet. In this report, we use mutagenesis and reporter gene assays to carry out a detailed analysis on the hinge region and the proximal ligand binding domain (LBD) of human ( h) LRH-1 that possess important regulatory functions. Our results indicate that helix 1 of the LBD is essential for the activity of hLRH-1 and that the steroid receptor coactivator (SRC)-1 interacts directly with the LBD of hLRH-1 and significantly potentiates the transcriptional activity of hLRH-1. Cotransfection assays demonstrate that overexpressed SRC-1 potentiates hLRH-1 mediated activation of the cholesterol 7-alpha-hydroxylase promoter and increases the transcription of the endogenous cholesterol 7-alpha-hydroxylase in Huh7 cells. The interaction between SRC-1 and hLRH-1 assumes a unique pattern that involves primarily a region containing the glutamine-rich domain of SRC-1, and helix 1 and activation function-2 of hLRH-1 LBD. Mutagenesis and molecular modeling studies indicate that, similar to mouse LRH-1, the coactivator-binding cleft of hLRH-1 LBD is not optimized. An interaction between helix 1 of hLRH-1 LBD and a region containing the glutamine-rich domain of SRC-1 can provide an additional stabilizing force and enhances the recruitment of SRC-1. Similar interaction is observed between hLRH-1 and SRC-2/transcriptional intermediary factor 2 or SRC-3/acetyltransferase. Moreover, transcriptional intermediary factor 2 and acetyltransferase also potentiate the transcriptional activity of hLRH-1, suggesting a functional redundancy among SRC family members. These findings collectively demonstrate an important functional role of helix 1 in cofactor recruitment and reveal a novel molecular mechanism of transcriptional regulation and cofactor recruitment mediated by hLRH-1. |
| 学科主题 | Endocrinology & Metabolism |
| 类目[WOS] | Endocrinology & Metabolism |
| 关键词[WOS] | THYROID-HORMONE RECEPTOR ; ORPHAN NUCLEAR RECEPTOR ; HEPATITIS-B-VIRUS ; FACTOR-I ; BINDING-PROTEIN ; HISTONE ACETYLTRANSFERASE ; ANDROGEN RECEPTOR ; P450SCC GENE ; ENHANCER II ; ACTIVATION |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000222907600003 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/2116]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Xu, PL,Liu, YQ,Shan, SF,et al. Molecular mechanism for the potentiation of the transcriptional activity of human liver receptor homolog 1 by steroid receptor coactivator-1[J]. MOLECULAR ENDOCRINOLOGY,2004,18(8):1887-1905. |
| APA | Xu, PL.,Liu, YQ.,Shan, SF.,Kong, YY.,Zhou, Q.,...&Wang, Y.(2004).Molecular mechanism for the potentiation of the transcriptional activity of human liver receptor homolog 1 by steroid receptor coactivator-1.MOLECULAR ENDOCRINOLOGY,18(8),1887-1905. |
| MLA | Xu, PL,et al."Molecular mechanism for the potentiation of the transcriptional activity of human liver receptor homolog 1 by steroid receptor coactivator-1".MOLECULAR ENDOCRINOLOGY 18.8(2004):1887-1905. |
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