APC/C- and Mad2-mediated degradation of Cdc20 during spindle checkpoint activation.
The spindle assembly checkpoint (SAC) is an important mechanism that prevents the separation of sister chromatids until the microtubules radiating from the spindle poles are correctly attached to the kinetochores. Cdc20, an activator of the Anaphase Promoting Complex/Cyclosome (APC/C), is known as a major downstream target for inhibition by the SAC through the binding of mitotic checkpoint proteins, such as Mad2 and BubR1. Here, we report that the SAC negatively regulates the stability of Cdc20 by targeting it for proteasome-dependent degradation. Once the checkpoint is activated by spindle poisons, a major population of Cdc20 is degraded via APC/C, an event that requires the binding of Cdc20 to Mad2. We propose that the degradation of Cdc20 represents a critical control mechanism to ensure inactivation of APC/C(Cdc20) in response to the SAC.
Ge
Sheng
S
Department of Pathology, NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Skaar
Jeffrey R
JR
Pagano
Michele
M
D064173:Anaphase-Promoting Complex-Cyclosome; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D064246:Mad2 Proteins; D008938:Mitosis / Q000187:drug effects; D050505:Mutant Proteins / Q000378:metabolism; D015739:Nocodazole / Q000494:pharmacology; D061988:Proteasome Inhibitors; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012097:Repressor Proteins / Q000378:metabolism*; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins; C577697:MAD2L1 protein, human; D064246:Mad2 Proteins; D050505:Mutant Proteins; D061988:Proteasome Inhibitors; D012097:Repressor Proteins; C577488:CDC20 protein, human; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D015739:Nocodazole