Figure 4

Rationales of enhancing ubiquitination. (A) Auxin is a plant hormone that directly binds to the F-box protein TIR1. With the support of co-factor InsP₆, auxin promotes TIR1 interaction with the substrate proteins, AUX/IAAs, leading to enhanced ubiquitination and degradation of substrates. (B) Binding of endogenous substrates to CRBN is blocked by IMiDs molecules, whereas IMiDs recruit neo-substrates (for example: IKZF1 and IKZF3) to CRBN, leading to the stabilization of endogenous substrates but degradation of neo-substrates.