title: Disassembly of mitotic checkpoint complexes by the joint action of the AAA-ATPase TRIP13 and p31(comet).
abstract: The mitotic (or spindle assembly) checkpoint system delays anaphase until all chromosomes are correctly attached to the mitotic spindle. When the checkpoint is active, a Mitotic Checkpoint Complex (MCC) assembles and inhibits the ubiquitin ligase Anaphase-Promoting Complex/Cyclosome (APC/C). MCC is composed of the checkpoint proteins Mad2, BubR1, and Bub3 associated with the APC/C activator Cdc20. When the checkpoint signal is turned off, MCC is disassembled and the checkpoint is inactivated. The mechanisms of the disassembly of MCC are not sufficiently understood. We have previously observed that ATP hydrolysis is required for the action of the Mad2-binding protein p31(comet) to disassemble MCC. We now show that HeLa cell extracts contain a factor that promotes ATP- and p31(comet)-dependent disassembly of a Cdc20-Mad2 subcomplex and identify it as Thyroid Receptor Interacting Protein 13 (TRIP13), an AAA-ATPase known to interact with p31(comet). The joint action of TRIP13 and p31(comet) also promotes the release of Mad2 from MCC, participates in the complete disassembly of MCC and abrogates checkpoint inhibition of APC/C. We propose that TRIP13 plays centrally important roles in the sequence of events leading to MCC disassembly and checkpoint inactivation.
authors.affiliation: Unit of Biochemistry, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel;
authors.forename: Esther
authors.initials: E
authors.lastname: Eytan
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, OH 43606; and.
authors.forename: Kexi
authors.initials: K
authors.lastname: Wang
authors.affiliation: Unit of Biochemistry, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel;
authors.forename: Shirly
authors.initials: S
authors.lastname: Miniowitz-Shemtov
authors.affiliation: Unit of Biochemistry, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel;
authors.forename: Danielle
authors.initials: D
authors.lastname: Sitry-Shevah
authors.affiliation: Unit of Biochemistry, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel;
authors.forename: Sharon
authors.initials: S
authors.lastname: Kaisari
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Yen
authors.affiliation: Department of Biological Sciences, University of Toledo, Toledo, OH 43606; and.
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Liu
authors.affiliation: Unit of Biochemistry, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel; hershko@tx.technion.ac.il.
authors.forename: Avram
authors.initials: A
authors.lastname: Hershko
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology*; D064199:Cdc20 Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D064246:Mad2 Proteins / Q000378:metabolism; D008938:Mitosis; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; C470309:MAD2L1BP protein, human; D064246:Mad2 Proteins; D009687:Nuclear Proteins; C577488:CDC20 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities; C575259:TRIP13 protein, human
keywords: mitosis; spindle checkpoint
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