title: Bod1 regulates protein phosphatase 2A at mitotic kinetochores.
abstract: Mitotic entry and progression require the activation of several mitotic kinases and the proper regulation and localization of several phosphatases. The activity and localization of each of these enzymes is tightly controlled through a series of specific activators, inhibitors and regulatory subunits. Two proteins, Ensa and Arpp-19, were recently identified as specific inhibitors of PP2A-B55 and are critical for allowing full activity of Cdk1/cyclin B and entry into mitosis. Here we show that Bod1, a protein required for proper chromosome alignment at mitosis, shares sequence similarity with Ensa and Arpp-19 and specifically inhibits the kinetochore-associated PP2A-B56 holoenzyme. PP2A-B56 regulates the stability of kinetochore-microtubule attachments by dephosphorylating several kinetochore proteins. Loss of Bod1 changes the balance of phosphorylation at kinetochores, causing defects in kinetochore function. Bod1, Ensa and Arpp-19 define a family of specific PP2A inhibitors that regulate specific PP2A holoenzymes at distinct locations and points in the cell cycle.
authors.affiliation: Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Iain M
authors.initials: IM
authors.lastname: Porter
authors.forename: Katharina
authors.initials: K
authors.lastname: Schleicher
authors.forename: Michael
authors.initials: M
authors.lastname: Porter
authors.forename: Jason R
authors.initials: JR
authors.lastname: Swedlow
mesh_terms: D000595:Amino Acid Sequence; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D002877:Chromosomes, Human / Q000378:metabolism / Q000648:ultrastructure; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism* / Q000648:ultrastructure; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008938:Mitosis; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000235:genetics* / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D059008:Time-Lapse Imaging
chemical_list: C524692:Bod1 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D010750:Phosphoproteins; D021122:Protein Subunits; C064321:cyclic AMP-regulated phosphoprotein 19; D016203:CDC2 Protein Kinase; D054648:Protein Phosphatase 2