Figure 1. Model illustrating multi-kinase–dependent Swe1 phosphorylation and degradation. In an early stage of the cell cycle, Cla4 phosphorylates Swe1 at the bud-neck, but this phosphorylation is not sufficient to trigger Swe1 degradation. Later in the cell cycle, such as in G2, Swe1 is moderately phosphorylated by nascent Clb2-Cdc28 activity, as the level of Clb2 rises in the nucleus, and this promotes Cdc5-dependent Swe1 hyper-phosphorylation and, subsequently, Swe1 degradation. Once unleashed from negative regulation by Swe1, the Clb2-Cdc28 complex becomes fully active and induces mitosis.