Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators.
Fiche publication
Date publication
juin 1998
Journal
The EMBO journal
Auteurs
Membres identifiés du Cancéropôle Est :
Pr CHAMBON Pierre, Dr VONESCH Jean-Luc, Mr LEROUGE Thierry
Tous les auteurs :
Huang N, vom Baur E, Garnier JM, Lerouge T, Vonesch JL, Lutz Y, Chambon P, Losson R
Lien Pubmed
Résumé
NSD1, a novel 2588 amino acid mouse nuclear protein that interacts directly with the ligand-binding domain (LBD) of several nuclear receptors (NRs), has been identified and characterized. NSD1 contains a SET domain and multiple PHD fingers. In addition to these conserved domains found in both positive and negative Drosophila chromosomal regulators, NSD1 contains two distinct NR interaction domains, NID-L and NID+L, that exhibit binding properties of NIDs found in NR corepressors and coactivators, respectively. NID-L, but not NID+L, interacts with the unliganded LBDs of retinoic acid receptors (RAR) and thyroid hormone receptors (TR), and this interaction is severely impaired by mutations in the LBD alpha-helix 1 that prevent binding of corepressors and transcriptional silencing by apo-NRs. NID+L, but not NID-L, interacts with the liganded LBDs of RAR, TR, retinoid X receptor (RXR), and estrogen receptor (ER), and this interaction is abrogated by mutations in the LBD alpha-helix 12 that prevent binding of coactivators of the ligand-induced transcriptional activation function AF-2. A novel variant (FxxLL) of the NR box motif (LxxLL) is present in NID+L and is required for the binding of NSD1 to holo-LBDs. Interestingly, NSD1 contains separate repression and activation domains. Thus, NSD1 may define a novel class of bifunctional transcriptional intermediary factors playing distinct roles in both the presence and absence of ligand.
Mots clés
Amino Acid Sequence, Animals, Base Sequence, COS Cells, cytology, Carrier Proteins, chemistry, Estrogen Receptor alpha, Gene Expression Regulation, Mice, Molecular Sequence Data, Nuclear Proteins, chemistry, Protein Conformation, Receptors, Cytoplasmic and Nuclear, chemistry, Receptors, Estrogen, metabolism, Receptors, Retinoic Acid, metabolism, Receptors, Thyroid Hormone, metabolism, Retinoic Acid Receptor alpha, Sequence Alignment, Sequence Homology, Amino Acid, Tretinoin, metabolism, Yeasts
Référence
EMBO J.. 1998 Jun;17(12):3398-412