Competition between thyroid hormone receptor-associated protein (TRAP) 220and transcriptional intermediary factor (TIF) 2 for binding to nuclear receptors - Implications for the recruitment of trap and P160 coactivator complexes

Transcriptional activation by nuclear receptors (NRs) involves the concerte d action of coactivators, chromatin components, and the basal transcription machinery. Crucial NR coactivators, which target primarily the conserved l igand-regulated activation (AF-2) domain, include p160 family members, such as TIF2, as well as p160-associated coactivators, such as CBP/p300. Becaus e these coactivators possess intrinsic histone acetyltransferase activity, they are believed to function mainly by regulating chromatin-dependent tran scriptional activation. Recent evidence suggests the existence of an additi onal NR coactivator complex, referred to as the thyroid hormone receptor-as sociated protein (TRAP) complex, which may function more directly as a brid ging complex to the basal transcription machinery. TRAP220, the 220-kDa NR- binding subunit of the complex, has been identified in independent studies using both biochemical and genetic approaches. In light of the functional d ifferences identified between p160 and TRAP coactivator complexes in NR act ivation, we have attempted to compare interaction and functional characteri stics of TIF 2 and TRAP220. Our findings imply that competition between the NR-binding subunits of distinct coactivator complexes may act as a putativ e regulatory step in establishing either a sequential activation cascade or the formation of independent coactivator complexes.