Activator-recruited cofactor

The DRIP (Vitamin D3 receptor [VDR] interacting proteins) complex was purified using a VDR ligand-binding domain affinity matrix (Rachez et al., 1998). DRIP is needed for full transcriptional activity of VDR on naked DNA templates in vitro. Another complex, ARC (activator-recruited cofactor), was identified as a complex that enhances transcription activation by SREBP-la, VP16, and the p65 subunit of NF-kappaB using chromatin-assembled DNA templates (Naar et al., 1999). Characterization of the subunits of DRIP and ARC showed that the two complexes are highly related—if not identical—to each other and also to the TRAP/SMCC complexes (Rachez et al., 1999). 

Collins HM, Kindle KB, Matsuda S, Ryan C, Troke PJ, Kalkhoven E, Heery DM (2006) MOZ-TIF2 alters cofactor recruitment and histone modification at the RARbeta 2 promoter Differential effects of MOZ fusion proteins on CBP-and MOZ-dependent activators. J Biol Chem 281 17124-17133... 

Activation of the caspases requires the help of a number of cofactors that are also known as activators or adaptors. Different cofactors are involved depending on the trigger mechanism of caspase activation. A central function of the cofactors is to bring about aggregation and thus activation of the procaspases. This occurs by specific protein-protein interactions with the help of common structural motives. Examples of such motives are the death domains (DD), death effector domains (DED) and the caspase recruitment domains (CARD), which all have a similar structure of six a-heh-ces. 

Binding of the ligand of the Fas receptor triggers clustering of the receptor and association of the cofactor FADD (fas-assodated protein with death domain) which interacts with the receptor via its death domain (DD). Procaspase 8 binds to FADD via a common DED (death effector domain) motif and is thereby also recruited into the Fas-receptor associated complex. Due to the clustering of the proteins, proximity-induced cleavage of procaspase 8 to the mature initiator caspase 8 takes place. This activates the effector caspases and triggers cell death. 

Fig. 4.11 Model of repression and activation of T3R. In the absence of the T3 hormone, a hetero-dimeric RXR-T3R receptor is bound at the T3-re-sponsive element,TRE, establishing a basal repressed state. The repressed state is maintained by recruitment of corepressor complexes containing histone deacetylase activity. X refers to potential unidentified cofactors (possibly chromatin remodeling complexes or SRBs) which help to keep the promotor-bound basal transcription apparatus in...

Recruitment of the initiator procaspases into a multiprotein complex results from a regulated series of protein-protein interactions mediated by interaction modules . Four types of interaction modules are involved in the activation of initiator caspases and thus play important roles in the initiation of apoptosis (review Weber and Vin-cenz, 2001). These domains have been named the death domain (DD),, the death effector domain (DED), the caspase activation and recruitment domain (CARD), and the less characterized pyrin domain. The domains are found on several components of the apoptotic signaling pathways and mediate homotypic protein-protein interactions, i. e., a given module will interact only with a member of the same family and not with members of the other families. Since members of the same module are found on different proteins, these modules mediate the assembly of hetero-oligomeric protein complexes. As examples, DDs are found on death receptors and their cofactors, D EDs on cofactors and the initiator caspase-8, and CARDS on cofactors, caspase-2, and caspase-9. 

---