The yeast Ada complex mediates the ligand-dependent activation function AF-2 of retinoid X and estrogen receptors
AUTOR(ES)
vom Baur, Elmar
FONTE
Cold Spring Harbor Laboratory Press
RESUMO
Nuclear receptors can function as ligand-inducible transregulators in both mammalian and yeast cells, indicating that important features of control of transcription have been conserved throughout evolution. Here, we report the isolation and characterization of a yeast protein that exhibits properties expected for a coactivator/mediator of the ligand-dependent activation function AF-2 present in the ligand-binding domain (LBD, region E) of the retinoid X (RXRα) and estrogen (ERα) receptors. This protein is identical to Ada3, a component of the yeast Ada coactivator complex. We demonstrate that: (1) the region encompassing residues 347–702 of Ada3 interacts with the LBD of RXRα and ERα in a ligand-dependent manner in yeast; (2) this interaction corresponds to a direct binding and requires the integrity of the core of the AF-2 activating domain (AF-2 AD) of both RXRα and ERα; (3) Ada3 as well as Ada2 and Gcn5, two other components of the Ada complex, are required for maximal AF-2 activity in yeast; and (4) Ada3 is able to enhance the AF-2 activity of RXRα and ERα when overexpressed in yeast and mammalian cells. Taken together, these data indicate that ligand-dependent transactivation by RXRα and ERα in yeast is mediated at least in part by the Ada complex, in which the Ada3 subunit directly binds to the holoreceptor LBD.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=316789Documentos Relacionados
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