Substrate degradation by the anaphase promoting complex occurs during mitotic slippage
| Autor: | Jinho Lee, Robert L. Margolis, Jin Ah Kim, Rati Fotedar |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cell cycle checkpoint
Cdc20 Proteins Ubiquitin-Protein Ligases Mitosis Antineoplastic Agents Cell Cycle Proteins Spindle Apparatus Biology Anaphase-Promoting Complex-Cyclosome Article S Phase Substrate Specificity chemistry.chemical_compound Antigens CD Humans Molecular Biology Kinetochore Nocodazole G1 Phase Ubiquitin-Protein Ligase Complexes Cell Biology Cadherins HCT116 Cells Cell biology Spindle apparatus Spindle checkpoint chemistry Mitotic exit Gene Knockdown Techniques Anaphase-promoting complex Developmental Biology |
| Zdroj: | Cell Cycle. 9:1792-1801 |
| ISSN: | 1551-4005 1538-4101 |
| DOI: | 10.4161/cc.9.9.11519 |
| Popis: | Microtubule targeting drugs are successful in chemotherapy because they indefinitely activate the spindle assembly checkpoint. The spindle assembly checkpoint monitors proper attachment of all kinetochores to microtubules and tension between the kinetochores of sister chromatids to prevent premature anaphase entry. To this end, the activated spindle assembly checkpoint suppresses the E3 ubiquitin ligase activity of the anaphase-promoting complex (APC). In the continued presence of conditions that activate the spindle assembly checkpoint, cells eventually escape from mitosis by “slippage”. It has not been directly tested whether APC activation accompanies slippage. Using cells blocked in mitosis with the microtubule assembly inhibitor nocodazole, we show that mitotic APC substrates are degraded upon mitotic slippage. To confirm that APC is normally activated upon mitotic slippage we have found that knockdown of Cdc20 and Cdh1, two mitotic activators of APC, prevents the degradation of APC substrates during mitotic slippage. We provide the first direct demonstration that despite conditions that activate the spindle checkpoint, APC is indeed activated upon mitotic slippage of cells to interphase cells. Activation of the spindle checkpoint by microtubule targeting drugs used in chemotherapy may not indefinitely prevent APC activation. |
| Databáze: | OpenAIRE |
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