Pathway of FBW7-mediated degradation. Proteins are targeted for degradation by the ubiquitin proteasome system through an enzymatic cascade involving three enzymes: the ubiquitin-activating E1, the ubiquitin-conjugating E2 and a ubiquitin ligase, E3. The initial step is ATP-dependent and involves the linkage of ubiquitin to E1. Ubiquitin is then activated and transferred to E2. The ubiquitin-charged E2 then interacts with a specific E3 partner such as SCF(FBW7), which transfers the ubiquitin molecule to the substrate, resulting in its recognition and degradation in an ATP-dependent manner by the 26S proteasome. FBW7, F-box and WD-repeat-domain-containing 7; Ub, ubiquitin.