title: Dual Regulation of the mitotic exit network (MEN) by PP2A-Cdc55 phosphatase.
abstract: Exit from mitosis in budding yeast is triggered by activation of the key mitotic phosphatase Cdc14. At anaphase onset, the protease separase and Zds1 promote the downregulation of PP2A(Cdc55) phosphatase, which facilitates Cdk1-dependent phosphorylation of Net1 and provides the first wave of Cdc14 activity. Once Cdk1 activity starts to decline, the mitotic exit network (MEN) is activated to achieve full Cdc14 activation. Here we describe how the PP2A(Cdc55) phosphatase could act as a functional link between FEAR and MEN due to its action on Bfa1 and Mob1. We demonstrate that PP2A(Cdc55) regulates MEN activation by facilitating Cdc5- and Cdk1-dependent phosphorylation of Bfa1 and Mob1, respectively. Downregulation of PP2A(Cdc55) initiates MEN activity up to Cdc15 by Bfa1 inactivation. Surprisingly, the premature Bfa1 inactivation observed does not entail premature MEN activation, since an additional Cdk1-Clb2 inhibitory signal acting towards Dbf2-Mob1 activity restrains MEN activity until anaphase. In conclusion, we propose a clear picture of how PP2A(Cdc55) functions affect the regulation of various MEN components, contributing to mitotic exit.
authors: Cell Cycle Group, Cancer Epigenetics and Biology Program (PEBC), Institut d'Investigacions Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.
authors: Barbara
authors: B
authors: Baro
authors: Jose-Antonio
authors: JA
authors: Rodriguez-Rodriguez
authors: Ines
authors: I
authors: Calabria
authors: María Luisa
authors: ML
authors: Hernáez
authors: Concha
authors: C
authors: Gil
authors: Ethel
authors: E
authors: Queralt
mesh_terms: D000705:Anaphase / Q000235:genetics*; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors; D015966:Gene Expression Regulation, Fungal; D008938:Mitosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000235:genetics* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D064247:Separase / Q000235:genetics
chemical_list: C119117:BFA1 protein, S cerevisiae; C074860:CDC14 protein, S cerevisiae; C071246:CDC55 protein, S cerevisiae; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C119300:Net1 protein, S cerevisiae; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D029701:Saccharomyces cerevisiae Proteins; D017346:Protein Serine-Threonine Kinases; C081927:CDC5 protein, S cerevisiae; D016203:CDC2 Protein Kinase; D054648:Protein Phosphatase 2; D017027:Protein Tyrosine Phosphatases; D064247:Separase