Mechanisms of Transcriptional Regulation by Nuclear Receptors

Multiple protein-protein interactions are involved in the transcription regulation by nuclear receptors. Nuclear receptors have been shown to directly interact with 

Most detailed information is available for the binding of coactivators and corepressors. 

A series of proteins or protein complexes with coactivator function for nuclear receptors has been identified that specifically interact with the activated, liganded receptor. The most abundant ones are now included in the pl60 family of coactivators with the steroid receptor coactivator 1, SRC-1, as a well-characterized member. Another group of coactivators is present as multiprotein complexes like the TRAP complex (TRAP, thyroid hormone receptor activating protein). A common receptor interaction motif LXXLL is found on these coactivators which mediates at least part of the interaction with the AF2 domain of the receptor. 

The pi60 coactivators themselves interact with other proteins or protein complexes with mediator function and histone acetylase activity. Particularly, an interaction with the CBP/p300 protein and the PCAF histone acetylase (see Section 1.4.6.) has been shown. It is thought that the primary function of the pl60 class of coactivators is 

Other types of coactivators include the CBP/p300 proteins themselves, which can also directly interact with DNA-bound receptors in a ligand-dependent manner. Members of the SWi/SNF complex and the E3 ubiquitin protein ligase E6-AP have also been recognized as having the function of coactivators of nuclear receptor function (review McKenna et al., 1999). 

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