TIF2, a 160 kDa transcriptional mediator for the ligand-dependent activation function AF-2 of nuclear receptors

EMBO J. 1996 Jul 15;15(14):3667-75.


Nuclear receptors (NRs) act as ligand-inducible transcription factors which regulate the expression of target genes upon binding to cognate response elements. The ligand-dependent activity of the NR activation function AF-2 is believed to be mediated to the transcription machinery through transcriptional mediators/intermediary factors (TIFs). We report here the cloning of the 160 kDa human nuclear protein TIF2, which exhibits all properties expected for a mediator of AF-2: (i) it interacts in vivo with NRs in an agonist-dependent manner; (ii) it binds directly to the ligand-binding domains (LBDs) of NRs in an agonist- and AF-2-integrity-dependent manner in vitro; (iii) it harbours an autonomous transcriptional activation function; (iv) it relieves nuclear receptor autosquelching; and (v) it enhances the activity of some nuclear receptor AF-2s when overexpressed in mammalian cells. TIF2 exhibits partial sequence homology with the recently isolated steroid receptor coactivator SRC-1, indicating the existence of a novel gene family of nuclear receptor transcriptional mediators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line, Transformed
  • Chlorocebus aethiops
  • DNA, Complementary
  • HeLa Cells
  • Humans
  • Ligands
  • Molecular Sequence Data
  • Nuclear Proteins / metabolism*
  • Nuclear Receptor Coactivator 2
  • Promoter Regions, Genetic
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Cells, Cultured


  • DNA, Complementary
  • Ligands
  • NCOA2 protein, human
  • Nuclear Proteins
  • Nuclear Receptor Coactivator 2
  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors

Associated data

  • GENBANK/X97674