Figure 2. Schematic illustration of CRL4A and CRL1^FBXO11-dependent ubiquitylation of Cdt2 and the regulation of various cellular activities. The scaffold CUL4A and CUL1 proteins (light green) in complex with the small RING finger protein (Rbx1/2) form the catalytic core of CRL4 and CRL1 (also known as SCF), respectively. CRL4A promotes the autoubiquitylation and degradation of the CUL4 substrate receptor Cdt2 (green).³⁹ The adaptor protein SKP1 (light blue) bridges CUL1 with the substrate receptor FBXO11 (beige), recognizing Cdt2 and promoting its ubiquitylation.^39,40 FBXO11-mediated ubiquitylation and degradation of Cdt2 is important for regulating cellular responses to TGF-β and cellular migration, primarily through its ability to upregulate Set8. It additionally regulates cell cycle progression (S and G₂) and promote exit from the cell cycle.