Deletion of APC7 or APC16 Allows Proliferation of Human Cells without the Spindle Assembly Checkpoint
| العنوان: | Deletion of APC7 or APC16 Allows Proliferation of Human Cells without the Spindle Assembly Checkpoint |
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| المؤلفون: | Thomas Wild, Marin Barisic, Chunaram Choudhary, Gopal Karemore, Susanne Hellmuth, Olaf Stemmann, Magda Budzowska, Susana Eibes |
| المصدر: | Cell Reports Wild, T, Budzowska, M, Hellmuth, S, Eibes, S, Karemore, G, Barisic, M, Stemmann, O & Choudhary, C 2018, ' Deletion of APC7 or APC16 Allows Proliferation of Human Cells without the Spindle Assembly Checkpoint ', Cell Reports, vol. 25, no. 9, 2317-2328.e5 . https://doi.org/10.1016/j.celrep.2018.10.104 |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Mad2, Cell Cycle Proteins, General Biochemistry, Genetics and Molecular Biology, Article, Anaphase-Promoting Complex-Cyclosome, 03 medical and health sciences, 0302 clinical medicine, Ubiquitin, APC16, Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome, APC/C, Humans, synthetic viability, Cyclin B1, MPS1, Mitosis, Genome stability, mass spectrometry, Cell Proliferation, mitosis, biology, Chemistry, Ubiquitination, HCT116 Cells, 3. Good health, Ubiquitin ligase, Cell biology, Spindle checkpoint, 030104 developmental biology, Mad2 Proteins, biology.protein, M Phase Cell Cycle Checkpoints, APC7, 030217 neurology & neurosurgery, Function (biology), MAD2, HeLa Cells |
| الوصف: | Summary The multisubunit ubiquitin ligase APC/C (anaphase-promoting complex/cyclosome) is essential for mitosis by promoting timely degradation of cyclin B1. APC/C is tightly regulated by the spindle assembly checkpoint (SAC), which involves MPS1 and MAD2-dependent temporal inhibition of APC/C. We analyzed the contribution of the APC/C subunits APC7 and APC16 to APC/C composition and function in human cells. APC16 is required for APC7 assembly into APC/C, whereas APC16 assembles independently of APC7. APC7 and APC16 knockout cells display no major defects in mitotic progression, cyclin B1 degradation, or SAC response, but APC/C lacking these two subunits shows reduced ubiquitylation activity in vitro. Strikingly, deletion of APC7 or APC16 is sufficient to provide synthetic viability to MAD2 deletion. ΔAPC7ΔMAD2 cells display accelerated mitosis and require SAC-independent MPS1 function for genome stability. These findings reveal that the composition of APC/C critically influences the importance of the SAC in humans. Graphical Abstract Highlights • APC16 is required for in vivo assembly of APC7 into APC/C • APC7 or APC16 deletion has no major effect on mitosis • Deletion of APC7 or APC16 provides synthetic viability to MAD2 deletion Anaphase-promoting complex/cyclosome (APC/C) is an essential regulator of mitosis in eukaryotes. Wild et al. show that the APC/C subunits APC7 and APC16 are not required for mitosis in normal cells. However, genetic deletion of these subunits provides synthetic viability to cells lacking the spindle assembly checkpoint. |
| وصف الملف: | application/pdf |
| تدمد: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2018.10.104 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::41e46910508083d8b178c4b1f184a377 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....41e46910508083d8b178c4b1f184a377 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22111247 |
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| DOI: | 10.1016/j.celrep.2018.10.104 |