Identity between TRAP and SMCC complexes indicates novel pathways for the function of nuclear receptors and diverse mammalian activators

The human thyroid hormone receptor-associated protein (TRAP) complex, an ea rlier described coactivator for nuclear receptors, and an SRB- and MED-cont aining cofactor complex (SMCC) that mediates activation by Ga14-p53 are sho wn to be virtually the same with respect to specific polypeptide subunits, coactivator functions, and mechanisms of action (activator interactions). I n parallel with ligand-dependent interactions of nuclear receptors with the TRAP220 subunit, p53 and VP16 activation domains interact directly with a newly cloned TRAP80 subunit. These results indicate novel pathways for the function of nuclear receptors and other activators (p53 and VP16) through a common coactivator complex that is likely to target RNA polymerase II. Ide ntification of the TRAP230 subunit as a previously predicted gene product a lso suggests a coactivator-related transcription defect in certain disease states.