Competition between thyroid hormone receptor-associated protein (TRAP) 220 and 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 concerted action of coactivators, chromatin components, and the basal transcription machinery. Crucial NR coactivators, which target primarily the conserved ligand-regulated activation (AF-2) domain, include p160 family members, such as TIF2, as well as p160-associated coactivators, such as CBP/p300. Because these coactivators possess intrinsic histone acetyltransferase activity, they are believed to function mainly by regulating chromatin-dependent transcriptional activation. Recent evidence suggests the existence of an additional NR coactivator complex, referred to as the thyroid hormone receptor-associated protein (TRAP) complex, which may function more directly as a bridging 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 differences identified between p160 and TRAP coactivator complexes in NR activation, we have attempted to compare interaction and functional characteristics of TIF 2 and TRAP220. Our findings imply that competition between the NR-binding subunits of distinct coactivator complexes may act as a putative regulatory step in establishing either a sequential activation cascade or the formation of independent coactivator complexes.
Treuter
E
E
Department of Biosciences at Novum, Karolinska Institute, S-14157 Huddinge, Sweden. eckardt.treuter@csb.ki.se
Johansson
L
L
Thomsen
J S
JS
Wärnmark
A
A
Leers
J
J
Pelto-Huikko
M
M
Sjöberg
M
M
Wright
A P
AP
Spyrou
G
G
Gustafsson
J A
JA
D000818:Animals; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D056913:Mediator Complex Subunit 1; D009687:Nuclear Proteins / Q000378:metabolism; D051958:Nuclear Receptor Coactivator 2; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D002352:Carrier Proteins; D018076:DNA, Complementary; C538855:MED1 protein, human; C538857:Med1 protein, rat; D056913:Mediator Complex Subunit 1; C498001:NCOA2 protein, human; C498003:Ncoa2 protein, rat; D009687:Nuclear Proteins; D051958:Nuclear Receptor Coactivator 2; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors