Regulating proteolysis. The figure shows how Ub-mediated proteolysis can be regulated by either regulating the activity of the E3 (A) or regulating the susceptibility of the target protein (B). (A) Activation of the APC during metaphase signals destruction of multiple proteins such as Pds1p and the B cyclins; the coordinated destruction of these proteins is used to drive multiple molecular events required for exit from mitosis. (B) Differential phosphorylation of the G1 cyclin Cln2p versus the Cdc42 effector Gic2p differentially affects their destruction by a common SCF complex: Cln2 is phosphorylated and unstable throughout G1, while Gic2p is phosphorylated, and destroyed, approaching the G1-to-S transition. See text for details.