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.

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