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

B Le Douarin; C Zechel; J M Garnier; Y Lutz; L Tora; P Pierrat; D Heery; H Gronemeyer; P Chambon; R Losson

doi:10.1002/j.1460-2075.1995.tb07194.x

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

EMBO J. 1995 May 1;14(9):2020-33. doi: 10.1002/j.1460-2075.1995.tb07194.x.

Authors

B Le Douarin¹, C Zechel, J M Garnier, Y Lutz, L Tora, P Pierrat, D Heery, H Gronemeyer, P Chambon, R Losson

Affiliation

¹ Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, Illkirch, Strasbourg.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Base Sequence
Biological Evolution
Cloning, Molecular
Conserved Sequence
DNA, Complementary / genetics
DNA, Fungal / genetics
Ligands
Mice
Molecular Sequence Data
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Protein Serine-Threonine Kinases / genetics*
Protein Serine-Threonine Kinases / metabolism
Proto-Oncogene Proteins / genetics*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-raf
Receptors, Cytoplasmic and Nuclear / metabolism
Receptors, Retinoic Acid / metabolism
Retinoid X Receptors
Saccharomyces cerevisiae / genetics
Saccharomyces cerevisiae / metabolism
Sequence Homology, Amino Acid
Transcription Factors / genetics*
Transcription Factors / metabolism

Substances

DNA, Complementary
DNA, Fungal
Ligands
Nuclear Proteins
Proto-Oncogene Proteins
Receptors, Cytoplasmic and Nuclear
Receptors, Retinoic Acid
Retinoid X Receptors
Transcription Factors
transcriptional intermediary factor 1
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins c-raf

Associated data

GENBANK/S78219
GENBANK/S78221