title: Transcriptional intermediary factor 1alpha mediates physical interaction and functional synergy between the coactivator-associated arginine methyltransferase 1 and glucocorticoid receptor-interacting protein 1 nuclear receptor coactivators.
abstract: In previous studies transcriptional intermediary factor 1alpha (TIF1alpha) was identified as a direct binding partner and potential transcriptional coactivator for nuclear receptors (NRs) but its overexpression inhibited, rather than enhanced, transcriptional activation by NRs. Here we show that TIF1alpha bound to and enhanced the function of the C-terminal activation domain (AD) of coactivator associated arginine methyltransferase 1 (CARM1) and the N-terminal AD of glucocorticoid receptor-interacting protein 1 (GRIP1). Furthermore, although TIF1alpha had little or no NR coactivator activity by itself, it cooperated synergistically with GRIP1 and CARM1 to enhance NR-mediated transcription. Inhibition of endogenous TIF1alpha expression reduced transcriptional activation by the GRIP1 N-terminal domain but not by the CARM1 C-terminal domain, suggesting that TIF1alpha may be more important for mediating the activity of the former than the latter. Reduction of endogenous TIF1alpha levels also compromised the androgen-dependent induction of an endogenous target gene of the androgen receptor. Finally, TIF1alpha formed a ternary complex with the GRIP1 N-terminal and CARM1 C-terminal domains. Thus, we conclude that TIF1alpha cooperates with NR coactivators GRIP1 and CARM1 by forming a stable ternary complex with them and enhancing the AD function of one or both of them.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Southern California, Los Angeles 90089, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Teyssier
authors.forename: Chen-Yin
authors.initials: CY
authors.lastname: Ou
authors.forename: Konstantin
authors.initials: K
authors.lastname: Khetchoumian
authors.forename: Régine
authors.initials: R
authors.lastname: Losson
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stallcup
mesh_terms: D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D051958:Nuclear Receptor Coactivator 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; C491310:GRIP1 protein, human; C498001:NCOA2 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D014157:Transcription Factors; C093517:transcriptional intermediary factor 1; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1