title: The PP2AB56phosphatase promotes the association of Cdc20 with APC/C in mitosis.
abstract: PP2A comprising B56 regulatory subunit isoforms (PP2AB56) is a serine/threonine phosphatase essential for mitosis. At the kinetochore, PP2AB56both stabilizes microtubule binding and promotes silencing of the spindle assembly checkpoint (SAC) through its association with the SAC protein BubR1. Cells depleted of the B56 regulatory subunits of PP2A are delayed in activation of Cdc20-containing APC/C (APC/CCdc20), which is an essential step for mitotic exit. It has been hypothesized that this delay arises from increased production of the mitotic checkpoint complex (MCC), an APC/CCdc20inhibitor formed at unattached kinetochores through SAC signaling. In contrast to this prediction, we show that depletion of B56 subunits does not increase the amount or stability of the MCC. Rather, delays in APC/CCdc20activation in B56-depleted cells correlate with impaired Cdc20 binding to APC/C. Stimulation of APC/CCdc20assembly does not require binding between PP2AB56and BubR1, and thus this contribution of PP2AB56towards mitotic exit is distinct from its functions at kinetochores. PP2AB56associates with APC/C constitutively in a BubR1-independent manner. A mitotic phosphorylation site on Cdc20, known to be a substrate of PP2AB56, modulates APC/CCdc20assembly. These results elucidate the contributions of PP2AB56towards completion of mitosis.
authors.affiliation: Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Sun Joo
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Veronica
authors.initials: V
authors.lastname: Rodriguez-Bravo
authors.affiliation: Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Hyunjung
authors.identifier: 0000-0003-1318-7153
authors.initials: H
authors.lastname: Kim
authors.affiliation: Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Sutirtha
authors.initials: S
authors.lastname: Datta
authors.affiliation: Cell Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA foleye1@mskcc.org.
authors.forename: Emily A
authors.identifier: 0000-0003-4870-558X
authors.initials: EA
authors.lastname: Foley
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism*; D064199:Cdc20 Proteins / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D064199:Cdc20 Proteins; C525690:PPP2R5A protein, human; D010768:Phosphoserine; D064173:Anaphase-Promoting Complex-Cyclosome; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases; D054648:Protein Phosphatase 2
keywords: APC/C; B56; Cdc20; Mitosis; PP2A