DDB1/Cereblon (CRBN)

Cereblon (CRBN) is the substrate recognition component of DCX (DDB1-CUL4-X-box) E3 Ubiquitin ligase complexes that mediates the ubiquitination of numerous target proteins such as ILF2 and MEIS2. Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1. 

In vivo, the endogenous substrate of CRBN MEIS2 is blocked from binding by immunomodulatory drugs (IMiDs), i.e. Thalidomide, which instead promotes the recruitment of IKZF1 or IKZF3 for degradation. DDB1 and CRBN complex has been co-expressed and purified from insect cells Sf9.