Identification of a MAD2-binding protein, CMT2, and its role in mitosis.
MAD2 is a key component of the spindle checkpoint that delays the onset of anaphase until all the kinetochores are attached to the spindle. It binds to human p55CDC and prevents it from promoting destruction of an anaphase inhibitor, securin. Here we report the characterization of a novel MAD2-binding protein, CMT2. Upon the completion of spindle attachment, formation of the CMT2-MAD2 complex coincides with dissociation of the p55CDC-MAD2 complex. Overexpression of CMT2 in cells arrested by the spindle checkpoint causes premature destruction of securin and allows exit from mitosis without chromosome segregation. Depletion of CMT2 induces cell death following a transient delay in the onset of anaphase. These results indicate that CMT2 interacts with the spindle checkpoint and coordinates cell cycle events in late mitosis.
Habu
Toshiyuki
T
Department of Radiation Oncology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Kim
Sang Hoon
SH
Weinstein
Jasminder
J
Matsumoto
Tomohiro
T
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D064199:Cdc20 Proteins; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D064246:Mad2 Proteins; D051379:Mice; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D011506:Proteins / Q000378:metabolism; D016415:Sequence Alignment; D008941:Spindle Apparatus / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D064199:Cdc20 Proteins; C577491:Cdc20 protein, mouse; D018797:Cell Cycle Proteins; D005656:Fungal Proteins; C470309:MAD2L1BP protein, human; D064246:Mad2 Proteins; C577698:Mad2l1 protein, mouse; C577699:Mad2l2 protein, mouse; D009687:Nuclear Proteins; D011506:Proteins; C577488:CDC20 protein, human