CID, Chemical Inducers of Dimerization

Fig. 7.12. Structures of several of the small molecules used as Chemical Inducers of Dimerizations (CIDs) in the three-hybrid systems to date.

Chemical inducers of dimerization (CID) are bivalent small molecules that bind t vo proteins simultaneously. The purpose of these molecules is to bring the proteins together to induce signal transduction [27]. For brevity, we will limit our discussion to CIDs that directly control transcription. The basic architecture of these systems consists of two chimeric proteins. The first contains a DNA-binding domain (DBD) fused to a ligand-binding domain (LBD) and the second chimera contains an LBD and an activation domain (AD). The small molecule that binds both of these proteins simultaneously induces proximity of the two proteins, resulting in transcription activation (Fig. 8.11). 

Fig.8.n Chemical inducers of dimerization (CID) to control transcription. This system requires two chimeric proteins, one comprising a DNA-binding domain (DBD) fused to a ligand-binding domain (LBD), and the other comprising an LBD fused to a transcriptional... 

Just as a dimeric RNA molecule can be introduced to mediate the interaction between the DNA-binding and ADs, so can a dimeric small molecule [17]. In fact, well before their use in a small molecule three-hybrid assay, dimeric small molecules were used as chemical inducers of dimerization (CIDs) to artificially oligomerize fusion proteins in vivo [18]. In the yeast three-hybrid system, the union of two protein fusions and a CID reconstitute the transcription of a reporter gene (Fig. 4.1-3(d)). In 1996, Licitra and Liu built what they called a yeast three-hybrid assay [19]. This assay consists of two fusion proteins and a heterodimeric small molecule CID that brings these fusion proteins together to activate the transcription of a reporter gene (Fig. 4.1-3 d)). 

Examples of small molecules, altered cell culture conditions, proteins, and genetic constructs used to probe RME. CID chemical inducer of dimerization. 

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