Figure 4.

Model of KRPs controlling the switch between the different cell cycle programs. A, In proliferating cells, B-type CDKs phosphorylate KRPs, triggering their destruction. In addition, phosphorylation might change the conformation of KRPs, interfering with their binding to A-type CDKs. B, In cells triggered to endoreduplicate, B-type CDK activity ceases, resulting in a stabilization of the KRPs, which now bind and inhibit A-type CDK-cyclin complexes with a role in mitosis. The KRP concentration, however, is probably not high enough to inhibit as well the CDK-cyclin complexes driving S-phase entry, allowing cells to reenter the S-phase. C, During cell cycle exit, KRP expression is up-regulated. Now, in addition to blocking entry into mitosis, CDK-cyclin complexes controlling the entry into S-phase become inhibited, resulting in a complete cell cycle arrest.