Kinase Activity of Fission Yeast Mph1 Is Required for Mad2 and Mad3 to Stably Bind the Anaphase Promoting Complex
| العنوان: | Kinase Activity of Fission Yeast Mph1 Is Required for Mad2 and Mad3 to Stably Bind the Anaphase Promoting Complex |
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| المؤلفون: | Atlanta G. Cook, Kevin G. Hardwick, Juri Rappsilber, Laura Milne, Alicja M. Sochaj, Judith Zich, Heather M. Syred, Hiro Ohkura |
| المصدر: | Current Biology Zich, J, Sochaj, A M, Syred, H M, Milne, L, Cook, A G, Ohkura, H, Rappsilber, J & Hardwick, K G 2012, ' Kinase Activity of Fission Yeast Mph1 Is Required for Mad2 and Mad3 to Stably Bind the Anaphase Promoting Complex ', Current Biology, vol. 22, no. 4, pp. 296–301 . https://doi.org/10.1016/j.cub.2011.12.049Test |
| بيانات النشر: | Elsevier Ltd. |
| مصطلحات موضوعية: | Cell cycle checkpoint, Mad2, Cdc20 Proteins, BUB1, Cell Cycle Proteins, Protein Serine-Threonine Kinases, Biology, Anaphase-Promoting Complex-Cyclosome, Mass Spectrometry, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Aurora Kinases, Report, Schizosaccharomyces, Phosphorylation, Kinetochores, 030304 developmental biology, 0303 health sciences, Agricultural and Biological Sciences(all), Kinetochore, Biochemistry, Genetics and Molecular Biology(all), Nuclear Proteins, Ubiquitin-Protein Ligase Complexes, Mitotic checkpoint complex, G2-M DNA damage checkpoint, Molecular biology, 3. Good health, Cell biology, Spindle checkpoint, Mad2 Proteins, M Phase Cell Cycle Checkpoints, Schizosaccharomyces pombe Proteins, Anaphase-promoting complex, Anaphase, General Agricultural and Biological Sciences, Protein Kinases, 030217 neurology & neurosurgery, Signal Transduction |
| الوصف: | Summary Defects in chromosome segregation result in aneuploidy, which can lead to disease or cell death [1, 2]. The spindle checkpoint delays anaphase onset until all chromosomes are attached to spindle microtubules in a bipolar fashion [3, 4]. Mad2 is a key checkpoint component that undergoes conformational activation, catalyzed by a Mad1-Mad2 template enriched at unattached kinetochores [5]. Mad2 and Mad3 (BubR1) then bind and inhibit Cdc20 to form the mitotic checkpoint complex (MCC), which binds and inhibits the anaphase promoting complex (APC/C). Checkpoint kinases (Aurora, Bub1, and Mps1) are critical for checkpoint signaling, yet they have poorly defined roles and few substrates have been identified [6–8]. Here we demonstrate that a kinase-dead allele of the fission yeast MPS1 homolog (Mph1) is checkpoint defective and that levels of APC/C-associated Mad2 and Mad3 are dramatically reduced in this mutant. Thus, MCC binding to fission yeast APC/C is dependent on Mph1 kinase activity. We map and mutate several phosphorylation sites in Mad2, producing mutants that display reduced Cdc20-APC/C binding and an inability to maintain checkpoint arrest. We conclude that Mph1 kinase regulates the association of Mad2 with its binding partners and thereby mitotic arrest. Graphical Abstract Highlights ► Mph1 kinase activity is required for stable binding of Mad2/3 to Cdc20Slp1-APC/C ► Mph1 kinase phosphorylates Mad2 ► mad2-S92A has reduced APC/C binding and is unable to maintain checkpoint arrest ► mad2-S187D suggests a possible role for Mph1 kinase in checkpoint inhibition |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0960-9822 |
| DOI: | 10.1016/j.cub.2011.12.049 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b422babab53da54d1e50ca17232280bTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4b422babab53da54d1e50ca17232280b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09609822 |
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| DOI: | 10.1016/j.cub.2011.12.049 |