Tip60 is a co-activator specific for class I nuclear hormone receptors

J Biol Chem. 2001 Dec 14;276(50):46841-8. doi: 10.1074/jbc.M103710200. Epub 2001 Oct 8.


The nuclear hormone receptor superfamily is composed of a group of hormone-dependent transcription factors that play prominent roles in homeostatic events in vertebrates. A prerequisite for steroid hormone receptor activity is the binding of co-activator molecules to the activation function-2 domain of the receptor. The LXXLL motif/nuclear receptor box, contained within a number of co-activator molecules, mediates the interaction with nuclear hormone receptors. Tip60 (Tat-interactive protein 60 kDa), previously shown to bind to and enhance androgen receptor (AR)-mediated transactivation, contains a single nuclear receptor box at its extreme C terminus. We demonstrate that unlike members of the p160 co-activator family that interact predominantly with the N terminus of the AR in an LXXLL motif-independent manner, the LXXLL motif of Tip60 is required and is sufficient for AR interaction. Furthermore, by using the mammalian two-hybrid system and transient transfection experiments, we show that Tip60 preferentially interacts with and up-regulates class I nuclear receptors, suggesting that Tip60 is a steroid hormone receptor-specific co-activator. We conclude that Tip60 may specifically regulate a subset of nuclear hormone receptors, giving an indication to how regulated nuclear receptor activation can be achieved.

MeSH terms

  • Acetyltransferases / metabolism*
  • Acetyltransferases / physiology*
  • Amino Acid Motifs
  • Animals
  • COS Cells
  • Cell Nucleus / metabolism*
  • Dimerization
  • Histone Acetyltransferases
  • Leucine / chemistry
  • Ligands
  • Lysine Acetyltransferase 5
  • Mutagenesis, Site-Directed
  • Mutation
  • Plasmids / metabolism
  • Polymerase Chain Reaction
  • Precipitin Tests
  • Protein Binding
  • Protein Biosynthesis
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / metabolism*
  • Transcription, Genetic
  • Transcriptional Activation
  • Two-Hybrid System Techniques
  • Up-Regulation


  • Ligands
  • Receptors, Cell Surface
  • Acetyltransferases
  • Histone Acetyltransferases
  • KAT5 protein, human
  • Lysine Acetyltransferase 5
  • Leucine