title: Nuclear PP2A-Cdc55 prevents APC-Cdc20 activation during the spindle assembly checkpoint.
abstract: Cdc55, a regulatory B-subunit of protein phosphatase 2A (PP2A) complex, is essential for the spindle assembly checkpoint (SAC) in budding yeast, but the regulation and molecular targets of PP2A-Cdc55 have not been clearly defined or are controversial. Here, we show that an important target of Cdc55 in the SAC is the anaphase-promoting complex (APC) coupled with Cdc20 and that APC-Cdc20 is kept inactive by dephosphorylation by nuclear PP2A-Cdc55 when spindle is damaged. By isolating a new class of Cdc55 mutants specifically defective in the SAC and by artificially manipulating nucleocytoplasmic distribution of Cdc55, we further show that nuclear Cdc55 is essential for the SAC. Because the Cdc55-binding proteins Zds1 and Zds2 inhibit both nuclear accumulation of Cdc55 and SAC activity, we propose that spatial control of PP2A by Zds1 family proteins is important for tight control of SAC and mitotic progression.
authors.affiliation: Department of Biology and Rosenstiel Basic Biomedical Sciences Research Center, Brandeis University, 415 South Street, Waltham, MA 02454, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Rossio
authors.forename: Takeshi
authors.initials: T
authors.lastname: Michimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.forename: Iwai
authors.initials: I
authors.lastname: Ohbayashi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kikuchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D064173:Anaphase-Promoting Complex-Cyclosome / Q000235:genetics / Q000378:metabolism*; D064199:Cdc20 Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000201:enzymology / Q000378:metabolism*
chemical_list: C071246:CDC55 protein, S cerevisiae; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D064173:Anaphase-Promoting Complex-Cyclosome; D054648:Protein Phosphatase 2
keywords: APC; Anaphase-promoting complex; Cdc55; PP2A; Protein phosphatase 2A; SAC; Spindle assembly checkpoint; Zds1