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.
Mesh Terms:
Calcium-Binding Proteins, Cell Cycle Proteins, Cell Line, Tumor, Humans, Mitosis, Mitotic Spindle Apparatus, Mutant Proteins, Nocodazole, Proteasome Endopeptidase Complex, Protein Binding, Protein Processing, Post-Translational, Repressor Proteins, Ubiquitin-Protein Ligase Complexes
Calcium-Binding Proteins, Cell Cycle Proteins, Cell Line, Tumor, Humans, Mitosis, Mitotic Spindle Apparatus, Mutant Proteins, Nocodazole, Proteasome Endopeptidase Complex, Protein Binding, Protein Processing, Post-Translational, Repressor Proteins, Ubiquitin-Protein Ligase Complexes
Cell Cycle
Date: Jan. 01, 2009
PubMed ID: 19098431
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