Ligand-dependent interaction of nuclear receptors with potential transcriptional intermediary factors (mediators)
| Autor: | B Le Douarin, David M. Heery, Régine Losson, Hinrich Gronemeyer, E. Vom Baur, Matthias J.S. Heine, Valérie Vivat, Pierre Chambon, C. Zechel |
|---|---|
| Rok vydání: | 1996 |
| Předmět: |
Transcriptional Activation
Transcription Genetic Receptors Retinoic Acid Molecular Sequence Data Retinoic acid Receptors Cytoplasmic and Nuclear Saccharomyces cerevisiae Retinoid X receptor Biology Transfection Calcitriol receptor General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Mice Mediator Genes Reporter Animals Receptor Cell Nucleus Binding Sites Receptors Thyroid Hormone Base Sequence Retinoic Acid Receptor alpha Recombinant Proteins Retinoid X Receptors Nuclear receptor Amphipathic Alpha Helix chemistry Biochemistry Receptors Estrogen Retinoic acid receptor alpha Receptors Calcitriol General Agricultural and Biological Sciences Transcription Factors |
| Zdroj: | Philosophical transactions of the Royal Society of London. Series B, Biological sciences. 351(1339) |
| ISSN: | 0962-8436 |
| Popis: | The activity of the ligand-inducible activation function 2 (AF-2) contained in the ligand binding domain (LBD) of nuclear receptors (NRs) is thought to be mediated by transcriptional intermediary factors (TIFs). We have recently reported the isolation and characterization of two novel mouse proteins, designated TIF1 and mSUG1, that interact in a ligand-dependent fashion with the LBD (region E) of several NRs in vivo as well as in vitro. Remarkably, these interactions require the conserved core motif of the AF-2 activating domain (AF-2 AD) and can be blocked by AF-2 antagonists. TIF1 and mSUG1 might therefore represent TIFs/mediators for the ligand-dependent AF-2 of NRs. By comparing the interaction properties of these two putative TIFs with different NRs including the oestrogen (ER), thyroid hormone (TR), vitamin D3 (VDR), retinoic acid (RAR alpha) and retinoid X (RXR) receptors, we demonstrate that: (i) RXR alpha efficiently interacts with TIF1, but not with mSUG1, whereas TR alpha interacts much more efficiently with mSUG1 than with TIF1, and RAR alpha, VDR and ER efficiently interact with both TIF1 and mSUG1; (ii) the amphipathic alpha helix core of AF-2 AD is differentially involved in the interactions of RAR alpha with TIF1 and mSUG1; and (iii) the AF-2 AD cores of RAR alpha and ER are similarly involved in their interaction with TIF1, but not with mSUG1. Thus the interaction interfaces between the various NRs and either TIF1 or mSUG1 may vary depending on the nature of both the receptor and the putative mediator of its AF-2 function. We discuss the possible roles of TIF1 and mSUG1 as mediators of the transcriptional activity of the AF-2 of NRs. |
| Databáze: | OpenAIRE |
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