title: Tip60 is a nuclear hormone receptor coactivator.
abstract: The androgen receptor (AR) is a member of the nuclear hormone receptor superfamily. Recent work in this field has been focused upon defining the mechanisms of transcriptional control exacted by members of this superfamily. Using a COOH-terminal region of the human AR in a yeast two-hybrid screen, we have identified Tip60 as an AR-interacting protein. In this report, we show that Tip60, which was originally identified as a coactivator for the human immunodeficiency virus TAT protein, can enhance AR-mediated transactivation in a ligand-dependent manner in LNCaP and COS-1 cell lines. In addition, our experiments show that Tip60 can also enhance transactivation through the estrogen receptor and progesterone receptor in a ligand-dependent manner; thus identifying Tip60 as a nuclear hormone receptor coactivator. Our studies also demonstrate that Tip60 co-immunoprecipitates with the full-length AR in vitro and that, in our system, Tip60 enhances transactivation to levels observed with the coactivators steroid receptor coactivator 1, p300, and CREB-binding protein. The importance of such proteins in enhancing nuclear hormone receptor-mediated transcriptional activation is widely accepted, and this work suggests that Tip60 may have an equally important role to play.
authors.affiliation: Prostate Research Group, Department of Surgery, Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne NE2 4HH, United Kingdom.
authors.forename: M E
authors.initials: ME
authors.lastname: Brady
authors.forename: D M
authors.initials: DM
authors.lastname: Ozanne
authors.forename: L
authors.initials: L
authors.lastname: Gaughan
authors.forename: I
authors.initials: I
authors.lastname: Waite
authors.forename: S
authors.initials: S
authors.lastname: Cook
authors.forename: D E
authors.initials: DE
authors.lastname: Neal
authors.forename: C N
authors.initials: CN
authors.lastname: Robson
mesh_terms: D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D051548:Histone Acetyltransferases; D006801:Humans; D000074443:Lysine Acetyltransferase 5; D009687:Nuclear Proteins / Q000378:metabolism; D056920:Nuclear Receptor Coactivator 1; D011506:Proteins / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics*; D014162:Transfection; D015003:Yeasts; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
chemical_list: D000123:Acetyltransferases; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D000074443:Lysine Acetyltransferase 5; D009687:Nuclear Proteins; D056920:Nuclear Receptor Coactivator 1; D011506:Proteins; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D011980:Receptors, Progesterone; D015534:Trans-Activators; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C494363:CREBBP protein, human; C098489:KAT5 protein, human; C538859:NCOA1 protein, human