The FEAR network

Abstract

Mitosis is governed by the oscillation of cyclin dependent kinase (CDK) activity and ubiquitin-dependent proteolysis. Entry into mitosis is initiated by mitotic cyclin-CDK activation. Anaphase onset occurs upon activation of the Anaphase Promoting Complex/Cyclosome (APC/C), a ubiquitin ligase that promotes the destruction of the anaphase inhibitor Securin. Destruction of Securin initiates chromosome segregation by activation of the protease Separase, allowing it to cleave a subunit of the cohesin complexes that hold the duplicated sister chromatids together. Upon completion of nuclear division cells exit from mitosis, a process defined by the inactivation of CDKs, disassembly of the mitotic spindle, and cytokinesis. In the budding yeast S. cerevisiae, a signaling network known as the FEAR network is critical to ensure accurate anaphase chromosome segregation and the integration of this process with other anaphase events. Here, we summarize what is known about the regulation and function of the FEAR network in budding yeast and discuss the potential for conserved FEAR network functions in other eukaryotes.

Figure 1. Cdc14 regulation

Cdc14 release from the nucleolus during early anaphase is mediated by the FEAR network and results in a pulse of Cdc14 activity that coordinates multiple anaphase events. Cdc14 release from the nucleolus in late anaphase is mediated by the MEN and results in sustained Cdc14 activity and exit from mitosis.

Figure 2. FEAR network functions

Cdc14 released by the FEAR network coordinates multiple mitotic events.