AF-2 domain

The coactivator SRC-1 has been shown to interact with and promote the transcriptional activity of a number of nuclear receptors, including ERa (Mclnemey et al., 1996 Onate et al., 1995). More recently, we have demonstrated that SRC-1 also stimulates ERp activity through a direct interaction with its LBD, where the AF-2 domain resides (Tremblay et... 

Figure 1 Major functional domains of RAR and RXR. The N-terminal A/B segment encodes the activation function-1 (AF-1) domain. The C segment encodes the DNA-binding domain (DBD). The D segment encodes a flexible hinge region. The E segment encodes the ligand-binding domain (LBD) and the activation function-2 (AF-2) domain. The C-terminal tail, F domain, is present in some, but not all, of the receptors.

The pl60 family of coactivators including steroid receptor coactivator 1 (SRC-1), TIF/GRIP (SRC-2), and ACTR/pCIP (SRC-3) [24] stimulates the transcriptional activity of nuclear receptors. The pi60 family of coactivators has three LXXLL motifs in the receptor-interacting domain (RID) that interacts with the AF-2 domain of nuclear receptors. SRC-1 is a weak HAT that interacts with p300/CBP and recruits CARM-1. 

CAR and PXR also interact with POU domain proteins such as Pit-1 and Oct-1 [61]. The interactions between Pit-1 and nuclear receptors are ligand dependent, and helix 12 in AF-2 domain of receptors is involved. In the absence of a receptor ligand, Pit-1 inhibits PXR and CAR heterodimer formation with RXR. The POU domain proteins repression of PXR and CAR may involve HDAC. Conversely, CAR and PXR repress Pit-1 by competing for coactivators [61], POU domain proteins interact... 

Activity is also influenced by families of intermediary proteins that bind to AF-2 domains of the receptors and function as coactivators or corepressors of gene transcription [30, 31] Coactivators of retinoid-induced gene transcription include SRC-l/NCoA-1, TIF2/GRIP-1/ NCoA-2, and PCIP/ACTR/AIB1. Corepressor proteins include N-CoR, SMRT, and TRIP [32-36]. 

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