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

Cell Cycle. 2008 Sep 1;7(17):2720-6. doi: 10.4161/cc.7.17.6580. Epub 2008 Sep 10.

Abstract

The Forkhead transcription factor FoxM1 is required for the timely expression of many mitotic regulators, such as Cyclin B, Plk1, Aurora B and Cdc25B.(1-3) For this, FoxM1 is specifically activated in G(2) phase through Cyclin A/cdk2-dependent phosphorylation.(4-6) 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 G(1). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Anaphase
  • Antigens, CD
  • Cadherins / metabolism*
  • Cell Line, Tumor
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors / chemistry
  • Forkhead Transcription Factors / metabolism*
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Mitosis*
  • Protein Processing, Post-Translational*
  • Recombinant Fusion Proteins / metabolism
  • Thermodynamics
  • Ubiquitination

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • Forkhead Transcription Factors
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins