标题：The TRAP220 component of a thyroid hormone receptor- associated protein (TRAP) coactivator complex interacts directly with nuclear receptors in a ligand-dependent fashion
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：14
页码：7939-7944
DOI：10.1073/pnas.95.14.7939
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Cognate cDNAs are described for 2 of the 10 thyroid hormone receptor-associated proteins (TRAPs) that are immunopurified with thyroid hormone receptor (TR) from ligand-treated HeLa (-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 TR, and these interactions are mediated through the C terminus of TR and (at least in part) the LXXLL domains of TRAP220. TRAP220 also interacts with other nuclear receptors [vitamin D receptor, retinoic acid receptor , retinoid X receptor , peroxisome proliferation-activated receptor (PPAR) , PPAR{gamma} and, to a lesser extent, estrogen receptor] in a ligand-dependent manner, whereas TRAP100 shows only marginal interactions with estrogen receptor, retinoid X receptor , PPAR, and PPAR{gamma}. Consistent with these results, TRAP220 moderately stimulates human TR-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 (TR) and in cell free transcription systems (TR and vitamin D receptor). These studies indicate that TRAP220 plays a major role in anchoring other TRAPs to TR during the function of the TR-TRAP complex and, further, that TRAP220 (possibly along with other TRAPs) may be a global coactivator for the nuclear receptor superfamily.
