The DRIP complex and SRC-1/p160 coactivators share similar nuclear receptor binding determinants but constitute functionally distinct complexes
- PMID: 10733574
- PMCID: PMC85487
- DOI: 10.1128/MCB.20.8.2718-2726.2000
The DRIP complex and SRC-1/p160 coactivators share similar nuclear receptor binding determinants but constitute functionally distinct complexes
Abstract
Transcriptional activation requires both access to DNA assembled as chromatin and functional contact with components of the basal transcription machinery. Using the hormone-bound vitamin D(3) receptor (VDR) ligand binding domain (LBD) as an affinity matrix, we previously identified a novel multisubunit coactivator complex, DRIP (VDR-interacting proteins), required for transcriptional activation by nuclear receptors and several other transcription factors. In this report, we characterize the nuclear receptor binding features of DRIP205, a key subunit of the DRIP complex, that interacts directly with VDR and thyroid hormone receptor in response to ligand and anchors the other DRIP subunits to the nuclear receptor LBD. In common with other nuclear receptor coactivators, DRIP205 interaction occurs through one of two LXXLL motifs and requires the receptor's AF-2 subdomain. Although the second motif of DRIP205 is required only for VDR binding in vitro, both motifs are used in the context of an retinoid X receptor-VDR heterodimer on DNA and in transactivation in vivo. We demonstrate that both endogenous p160 coactivators and DRIP complexes bind to the VDR LBD from nuclear extracts through similar sequence requirements, but they do so as distinct complexes. Moreover, in contrast to the p160 family of coactivators, the DRIP complex is devoid of any histone acetyltransferase activity. The results demonstrate that different coactivator complexes with distinct functions bind to the same transactivation region of nuclear receptors, suggesting that they are both required for transcription activation by nuclear receptors.
Figures
![FIG. 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/85487/bin/mb0801997001.gif)
![FIG. 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/85487/bin/mb0801997002.gif)
![FIG. 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/85487/bin/mb0801997003.gif)
![FIG. 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/85487/bin/mb0801997004.gif)
![FIG. 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/85487/bin/mb0801997005.gif)
![FIG. 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/85487/bin/mb0801997006.gif)
![FIG. 7](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/85487/bin/mb0801997007.gif)
![FIG. 8](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/85487/bin/mb0801997008.gif)
Similar articles
-
Two distinct coactivators, DRIP/mediator and SRC/p160, are differentially involved in vitamin D receptor transactivation during keratinocyte differentiation.Mol Endocrinol. 2003 Nov;17(11):2329-39. doi: 10.1210/me.2003-0063. Epub 2003 Jul 31. Mol Endocrinol. 2003. PMID: 12893881
-
A novel protein complex that interacts with the vitamin D3 receptor in a ligand-dependent manner and enhances VDR transactivation in a cell-free system.Genes Dev. 1998 Jun 15;12(12):1787-800. doi: 10.1101/gad.12.12.1787. Genes Dev. 1998. PMID: 9637681 Free PMC article.
-
1alpha,25-dihydroxy vitamin D3-enhanced expression of the osteocalcin gene involves increased promoter occupancy of basal transcription regulators and gradual recruitment of the 1alpha,25-dihydroxy vitamin D3 receptor-SRC-1 coactivator complex.J Cell Physiol. 2008 Mar;214(3):740-9. doi: 10.1002/jcp.21267. J Cell Physiol. 2008. PMID: 17786964
-
The vitamin D hormone and its nuclear receptor: molecular actions and disease states.J Endocrinol. 1997 Sep;154 Suppl:S57-73. J Endocrinol. 1997. PMID: 9379138 Review.
-
The role of coactivators and corepressors in the biology and mechanism of action of steroid hormone receptors.J Mammary Gland Biol Neoplasia. 2000 Jul;5(3):307-24. doi: 10.1023/a:1009503029176. J Mammary Gland Biol Neoplasia. 2000. PMID: 14973393 Review.
Cited by
-
Role of Neural Stem Cells and Vitamin D Receptor (VDR)-Mediated Cellular Signaling in the Mitigation of Neurological Diseases.Mol Neurobiol. 2022 Jul;59(7):4065-4105. doi: 10.1007/s12035-022-02837-z. Epub 2022 Apr 27. Mol Neurobiol. 2022. PMID: 35476289 Review.
-
Discovery and Structure-Activity Relationships of Novel Template, Truncated 1'-Homologated Adenosine Derivatives as Pure Dual PPARγ/δ Modulators.J Med Chem. 2020 Dec 24;63(24):16012-16027. doi: 10.1021/acs.jmedchem.0c01874. Epub 2020 Dec 16. J Med Chem. 2020. PMID: 33325691 Free PMC article.
-
Molecular determinants of MED1 interaction with the DNA bound VDR-RXR heterodimer.Nucleic Acids Res. 2020 Nov 4;48(19):11199-11213. doi: 10.1093/nar/gkaa775. Nucleic Acids Res. 2020. PMID: 32990725 Free PMC article.
-
Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis.Int J Mol Sci. 2019 Oct 9;20(20):4986. doi: 10.3390/ijms20204986. Int J Mol Sci. 2019. PMID: 31600974 Free PMC article. Review.
-
Vitamin D: Effect on Haematopoiesis and Immune System and Clinical Applications.Int J Mol Sci. 2018 Sep 8;19(9):2663. doi: 10.3390/ijms19092663. Int J Mol Sci. 2018. PMID: 30205552 Free PMC article. Review.
References
-
- Armstrong J A, Emerson B M. Transcription of chromatin: these are complex times. Curr Opin Genet Dev. 1998;8:165–172. - PubMed
-
- Atkins G B, Guenther M G, Rachez C, Freedman L P, Lazar M A. Coactivators for the orphan nuclear receptor RORalpha. Mol Endocrinol. 1999;13:1550–1557. - PubMed
-
- Boyer T G, Martin M E, Lees E, Ricciardi R P, Berk A J. Mammalian Srb/Mediator complex is targeted by adenovirus E1A protein. Nature. 1999;399:276–279. - PubMed
-
- Chen H, Lin R J, Xie W, Wilpitz D, Evans R M. Regulation of hormone-induced histone hyperacetylation and gene activation via acetylation of an acetylase. Cell. 1999;98:675–686. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous