title: The ABBA motif binds APC/C activators and is shared by APC/C substrates and regulators.
abstract: The anaphase-promoting complex or cyclosome (APC/C) is the ubiquitin ligase that regulates mitosis by targeting specific proteins for degradation at specific times under the control of the spindle assembly checkpoint (SAC). How the APC/C recognizes its different substrates is a key problem in the control of cell division. Here, we have identified the ABBA motif in cyclin A, BUBR1, BUB1, and Acm1, and we show that it binds to the APC/C coactivator CDC20. The ABBA motif in cyclin A is required for its proper degradation in prometaphase through competing with BUBR1 for the same site on CDC20. Moreover, the ABBA motifs in BUBR1 and BUB1 are necessary for the SAC to work at full strength and to recruit CDC20 to kinetochores. Thus, we have identified a conserved motif integral to the proper control of mitosis that connects APC/C substrate recognition with the SAC.
authors: The Gurdon Institute and Department of Zoology, University of Cambridge, Cambridge, CB2 1QN, UK.
authors: Barbara
authors: B
authors: Di Fiore
authors: Department of Physiology and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158, USA.|Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Baden-Württemberg 69117, Germany.
authors: Norman E
authors: NE
authors: Davey
authors: The Gurdon Institute and Department of Zoology, University of Cambridge, Cambridge, CB2 1QN, UK.
authors: Anja
authors: A
authors: Hagting
authors: The Gurdon Institute and Department of Zoology, University of Cambridge, Cambridge, CB2 1QN, UK.
authors: Daisuke
authors: D
authors: Izawa
authors: Technische Universität Dresden, Tatzberg 47/49, 01307 Dresden, Germany.
authors: Jörg
authors: J
authors: Mansfeld
authors: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Baden-Württemberg 69117, Germany.
authors: Toby J
authors: TJ
authors: Gibson
authors: The Gurdon Institute and Department of Zoology, University of Cambridge, Cambridge, CB2 1QN, UK.
authors: Jonathon
authors: J
authors: Pines
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000378:metabolism*; D064199:Cdc20 Proteins / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
chemical_list: D064199:Cdc20 Proteins; C553801:MTSS2 protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; C584277:BUB1 protein, human; D017346:Protein Serine-Threonine Kinases