The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion.
Cognate cDNAs are described for 2 of the 10 thyroid hormone receptor-associated proteins (TRAPs) that are immunopurified with thyroid hormone receptor alpha (TRalpha) from ligand-treated HeLa (alpha-2) cells. Both TRAP220 and TRAP100 contain LXXLL domains found in other nuclear receptor-interacting proteins and both appear to reside in a single complex with other TRAPs (in the absence of TR). However, only TRAP220 shows a direct ligand-dependent interaction with TRalpha, and these interactions are mediated through the C terminus of TRalpha and (at least in part) the LXXLL domains of TRAP220. TRAP220 also interacts with other nuclear receptors [vitamin D receptor, retinoic acid receptor alpha, retinoid X receptor alpha, peroxisome proliferation-activated receptor (PPAR) alpha, PPARgamma and, to a lesser extent, estrogen receptor] in a ligand-dependent manner, whereas TRAP100 shows only marginal interactions with estrogen receptor, retinoid X receptor alpha, PPARalpha, and PPARgamma. Consistent with these results, TRAP220 moderately stimulates human TRalpha-mediated transcription in transfected cells, whereas a fragment containing the LXXLL motifs acts as a dominant negative inhibitor of nuclear receptor-mediated transcription both in transfected cells (TRalpha) and in cell free transcription systems (TRalpha and vitamin D receptor). These studies indicate that TRAP220 plays a major role in anchoring other TRAPs to TRalpha during the function of the TRalpha-TRAP complex and, further, that TRAP220 (possibly along with other TRAPs) may be a global coactivator for the nuclear receptor superfamily.
Yuan
C X
CX
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10021, USA.
Ito
M
M
Fondell
J D
JD
Fu
Z Y
ZY
Roeder
R G
RG
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism*; D003001:Cloning, Molecular; D006801:Humans; D008024:Ligands; D056913:Mediator Complex Subunit 1; D051379:Mice; D008969:Molecular Sequence Data; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; D000092468:Bromodomain Containing Proteins
D002352:Carrier Proteins; D008024:Ligands; D056913:Mediator Complex Subunit 1; D018160:Receptors, Cytoplasmic and Nuclear; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors; C099139:BRD8 protein, human; D000092468:Bromodomain Containing Proteins; C538855:MED1 protein, human; C538856:Med1 protein, mouse