Tip60 is a co-activator specific for class I nuclear hormone receptors.
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.
Gaughan
L
L
Prostate Research Group, School of Surgical Sciences, University of Newcastle upon Tyne Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, United Kingdom.
Brady
M E
ME
Cook
S
S
Neal
D E
DE
Robson
C N
CN
D000123:Acetyltransferases / Q000378:metabolism* / Q000502:physiology*; D020816:Amino Acid Motifs; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D019281:Dimerization; D051548:Histone Acetyltransferases; D007930:Leucine / Q000737:chemistry; D008024:Ligands; D000074443:Lysine Acetyltransferase 5; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques; D015854:Up-Regulation
D008024:Ligands; D011956:Receptors, Cell Surface; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C098489:KAT5 protein, human; D000074443:Lysine Acetyltransferase 5; D007930:Leucine