FoxM1 is degraded at mitotic exit in a Cdh1-dependent manner

Abstract

The Forkhead transcription factor FoxM1 is required for the timely expression of many mitotic regulators, such as Cyclin B, Plk1, Aurora B and Cdc25B1-3. For this, FoxM1 is specifically activated in G2 phase through Cyclin A/cdk2-dependent phosphorylation4-6. However, it is currently unclear how FoxM1 activity is removed as cells complete mitosis, and need to shut down expression of the mitotic regulators that are transcriptional targets of FoxM1. Here, we demonstrate that FoxM1 is actively degraded during exit from mitosis by the APC/C. We find that FoxM1 degradation requires Cdh1, a known co-factor for APC/C that is responsible for degradation of many mitotic regulators from anaphase until early G1. FoxM1 binds to Cdh1, and FoxM1 degradation involves both D- and KEN-boxes present in the N-terminal part of FoxM1. Based on these data we propose that Cdh1-dependent degradation of FoxM1 is required to shut down transcriptional activation of mitotic regulators during exit from mitosis.