Figure 2.

Illustration of ubiquitination cascade reactions, representative F-box protein and its major downstream targets involved in chemoresistance. E1 and E2 firstly activate and then transfer ubiquitin to the substrate at the help of E3. Ubiquitinated proteins can be recognized and degraded by the 26S proteasome. F-box protein in E3 determines the specificity of the target proteins in this process. SKP2 is the most profound one of FBXL family, the main targets of this family protein are p27, p21, Foxo1 and cyclin D1. FBXW7 is the representative of FBXW family, the main targets of this family protein are Nrf2, Mcl-1, CRY2 and NOTCH. FBXO31 is one member of FBXO family, the main targets of this family protein are P-gp, CD147 and Chk1.