title: TRIP13 Regulates Both the Activation and Inactivation of the Spindle-Assembly Checkpoint.
abstract: Biochemical studies have indicated that p31(comet) and TRIP13 are critical for inactivating MAD2. To address unequivocally whether p31(comet) and TRIP13 are required for mitotic exit at the cellular level, their genes were ablated either individually or together in human cells. Neither p31(comet) nor TRIP13 were absolutely required for unperturbed mitosis. MAD2 inactivation was only partially impaired in p31(comet)-deficient cells. In contrast, TRIP13-deficient cells contained MAD2 exclusively in the C-MAD2 conformation. Our results indicate that although p31(comet) enhanced TRIP13-mediated MAD2 conversion, it was not absolutely necessary for the process. Paradoxically, TRIP13-deficient cells were unable to activate the spindle-assembly checkpoint, revealing that cells lacking the ability to inactivate MAD2 were incapable in mounting a checkpoint response. These results establish a paradigm of the roles of p31(comet) and TRIP13 in both checkpoint activation and inactivation.
authors.affiliation: Division of Life Science, Center for Cancer Research and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
authors.forename: Hoi Tang
authors.initials: HT
authors.lastname: Ma
authors.affiliation: Division of Life Science, Center for Cancer Research and State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong. Electronic address: rycpoon@ust.hk.
authors.forename: Randy Yat Choi
authors.initials: RYC
authors.lastname: Poon
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D055786:Gene Knockout Techniques; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D064246:Mad2 Proteins / Q000737:chemistry / Q000378:metabolism; D008938:Mitosis; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; C470309:MAD2L1BP protein, human; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D000074183:ATPases Associated with Diverse Cellular Activities; C575259:TRIP13 protein, human
keywords: MAD2; mitosis; mitotic exit; p31(comet); spindle-assembly checkpoint