The N-terminal part of TIF1, a putative mediator of the ligand-dependent activation function (AF-2) of nuclear receptors, is fused to B-raf in the oncogenic protein T18.
Nuclear receptors (NRs) bound to response elements mediate the effects of cognate ligands on gene expression. Their ligand-dependent activation function, AF-2, presumably acts on the basal transcription machinery through intermediary proteins/mediators. We have isolated a mouse nuclear protein, TIF1, which enhances RXR and RAR AF-2 in yeast and interacts in a ligand-dependent manner with several NRs in yeast and mammalian cells, as well as in vitro. Remarkably, these interactions require the amino acids constituting the AF-2 activating domain conserved in all active NRs. Moreover, the oestrogen receptor (ER) AF-2 antagonist hydroxytamoxifen cannot promote ER-TIF1 interaction. We propose that TIF1, which contains several conserved domains found in transcriptional regulatory proteins, is a mediator of ligand-dependent AF-2. Interestingly, the TIF1 N-terminal moiety is fused to B-raf in the mouse oncoprotein T18.
Pubmed ID: 7744009 RIS Download
Amino Acid Sequence | Animals | Base Sequence | Biological Evolution | Cloning, Molecular | Conserved Sequence | DNA, Complementary | DNA, Fungal | Ligands | Mice | Molecular Sequence Data | Nuclear Proteins | Protein-Serine-Threonine Kinases | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-raf | Receptors, Cytoplasmic and Nuclear | Receptors, Retinoic Acid | Retinoid X Receptors | Saccharomyces cerevisiae | Sequence Homology, Amino Acid | Transcription Factors