title: Differential ligand-dependent interactions between the AF-2 activating domain of nuclear receptors and the putative transcriptional intermediary factors mSUG1 and TIF1.
abstract: Using a yeast two-hybrid system we report the isolation of a novel mouse protein, mSUG1, that interacts with retinoic acid receptor alpha (RAR alpha) both in yeast cells and in vitro in a ligand- and AF-2 activating domain (AF-2 AD)-dependent manner and show that it is a structural and functional homologue of the essential yeast protein SUG1. mSUG1 also efficiently interacts with other nuclear receptors, including oestrogen (ER), thyroid hormone (TR), Vitamin D3 (VDR) and retinoid X (RXR) receptors. By comparing the interaction properties of these receptors with mSUG1 and TIF1, 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 mSUG1 and TIF1; (ii) the amphipathic alpha-helix core of the AF-2 AD is differentially involved in interactions of RAR alpha with mSUG1 and TIF1; (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 different receptors and either mSUG1 or TIF1 may vary depending on the nature of the receptor and the putative mediator of its AF-2 function. We discuss the possibility that mSUG1 and TIF1 may mediate the transcriptional activity of the AF-2 of nuclear receptors through different mechanisms.
authors.affiliation: Institut de Génétique et de Biologie Moleculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, Cedex, France.
authors.forename: E
authors.initials: E
authors.lastname: vom Baur
authors.forename: C
authors.initials: C
authors.lastname: Zechel
authors.forename: D
authors.initials: D
authors.lastname: Heery
authors.forename: M J
authors.initials: MJ
authors.lastname: Heine
authors.forename: J M
authors.initials: JM
authors.lastname: Garnier
authors.forename: V
authors.initials: V
authors.lastname: Vivat
authors.forename: B
authors.initials: B
authors.lastname: Le Douarin
authors.forename: H
authors.initials: H
authors.lastname: Gronemeyer
authors.forename: P
authors.initials: P
authors.lastname: Chambon
authors.forename: R
authors.initials: R
authors.lastname: Losson
mesh_terms: D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D005656:Fungal Proteins / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D005656:Fungal Proteins; D009687:Nuclear Proteins; C085834:PA700 proteasome activator; D011506:Proteins; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C093517:transcriptional intermediary factor 1; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases; C069670:RPT6 protein, S cerevisiae