title: Positive feedback promotes mitotic exit via the APC/C-Cdh1-separase-Cdc14 axis in budding yeast.
abstract: The mitotic inhibitor securin is degraded via the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C)-Cdc20 after anaphase onset. This triggers activation of the mitotic protease separase and thereby sister chromatid separation. However, only a proportion of securin molecules are degraded at metaphase-anaphase transition and the remaining molecules are still present in anaphase. The roles of securin and separase in late mitosis remain elusive. Here, we show that securin still inhibits separase to repress mitotic exit in anaphase in budding yeast. APC/C-Cdh1-mediated securin degradation at telophase further liberated separase, which promotes Cdc14 release and mitotic exit. Separase executed these events via its proteolytic action and that in the Cdc14 early release (FEAR) network. Cdc14 release further activated APC/C-Cdh1 in the manner of a positive feedback loop. Thus, the positive feedback promotes mitotic exit via the APC/C-Cdh1-separase-Cdc14 axis. This study shows the importance of the two-step degradation mode of securin and the role of separase in mitotic exit.
authors.affiliation: Faculty of Biological Science, Shizuoka University, Shizuoka 422-8529, Japan.
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Hatano
authors.affiliation: Faculty of Biological Science, Shizuoka University, Shizuoka 422-8529, Japan.
authors.forename: Koike
authors.initials: K
authors.lastname: Naoki
authors.affiliation: Faculty of Biological Science, Shizuoka University, Shizuoka 422-8529, Japan.
authors.forename: Asuka
authors.initials: A
authors.lastname: Suzuki
authors.affiliation: Faculty of Biological Science, Shizuoka University, Shizuoka 422-8529, Japan. Electronic address: takashi.ushimaru@gmail.com.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ushimaru
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism*; D025461:Feedback, Physiological; D008938:Mitosis; D008954:Models, Biological; D011485:Protein Binding; D059748:Proteolysis; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D004718:Saccharomycetales / Q000166:cytology* / Q000378:metabolism*; D064249:Securin / Q000378:metabolism; D064247:Separase / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D064249:Securin; D064173:Anaphase-Promoting Complex-Cyclosome; D064247:Separase
keywords: APC/C-Cdh1; Budding yeast; Mitotic exit; Saccharomyces cerevisiae; Securin; Separase