title: CoCoA, a nuclear receptor coactivator which acts through an N-terminal activation domain of p160 coactivators.
abstract: The p160 coactivators bind to and potentiate transcriptional activation by nuclear receptors by recruiting secondary coactivators such as the histone acetyltransferases p300 and CBP and the protein methyltransferase CARM1. The function of the highly conserved N-terminal basic-helix-loop-helix/Per-Arnt-Sim (bHLH-PAS) domain of p160 coactivators is unknown. This region is required for coactivator synergy among p160, p300, and CARM1 coactivators. We identified a coactivator, coiled-coil coactivator (CoCoA), which binds to this domain and thereby enhances transcriptional activation by the estrogen receptor and other nuclear receptors. Endogenous CoCoA was found simultaneously with p160 coactivators on the promoter of an endogenous estrogen-responsive gene. Reduction of endogenous cellular CoCoA levels inhibited the estrogen-stimulated expression of transiently transfected and endogenous genes. Moreover, CoCoA cooperated synergistically with GRIP1, CARM1, and p300 to enhance ER-mediated transcription. Thus, the N-terminal region of p160 coactivators contains an additional activation domain which contributes to coactivator function by recruitment of CoCoA.
authors.affiliation: Department of Pathology, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Jeong Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stallcup
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D050881:E1A-Associated p300 Protein; D004967:Estrogens / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D051958:Nuclear Receptor Coactivator 2; D011401:Promoter Regions, Genetic; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011484:Protein-Arginine N-Methyltransferases / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
chemical_list: D004967:Estrogens; C498001:NCOA2 protein, human; C498002:Ncoa2 protein, mouse; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1; D050881:E1A-Associated p300 Protein; C494361:Ep300 protein, mouse