Figure 8.

Sustaining endocycles in the mouse trophectoderm lineage. Oscillation of APC activity and the levels of CDK-specific inhibitors and Geminin (Gmnn) are inversely related to oscillation of cyclin E (broken gray line). APC activity and CDK inhibitor levels are high in G phases but low in S phases, whereas cyclin E is low in G phases but high in S phases. Cdk2•CcnE activity is required to begin S phase. Endocycles result from a sequence of feedback loops, resulting from phosphorylation events by Cdk2•CcnE, and ubiquitination events by CRL1 and the APC. Ubiquitination by CRL1 requires prior CDK-dependent phosphorylation of its substrate. These events inhibit the activity of their protein targets and cause them to be degraded by the 26S proteasome (→ø). Protein names are those for mammals.