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Requirement for proteolysis in spindle assembly checkpoint silencing

阿平添加于 2010-3-10 20:12 | 2799 次阅读 | 0 个评论

作者
Visconti R, Palazzo L, Grieco D
摘要
Anaphase initiation requires ubiquitin-dependent proteolysis of crucial substrates through activation of the ubiquitin ligase Anaphase promoting Complex/Cyclosome (ApC/C) in association with its coactivator Cdc20. To prevent chromosome segregation errors, effector proteins of a safeguard mechanism called spindle assembly checkpoint (SAC), Mad2 and BubR1, bind Cdc20 and restrain ApC/C(Cdc20) activation until spindle assembly. Coordinated chromosome segregation also requires timely SAC inactivation. Spindle assembly appears necessary to silence SAC, however, how resolution of the SAC effector branch is achieved is still largely unknown. We show here that the complex between Mad2 and Cdc20 peaked at prometaphase in mammalian cells, while its dissociation proceeded along with spindle assembly and required proteolysis. proteolysis did not appear required for assembly of metaphase spindles but rather needed for Mad2-Cdc20 complex resolution by promoting reversal of phosphorylations that maintain the complex. Indeed, in the absence of proteolysis, Mad2-Cdc20 complex dissociation was reversed by treatment with cyclin-dependent kinase or Aurora kinase inhibitors. Mad2-Cdc20 disassembly was, however, resistant to the potent pp1 and pp2A phosphatases inhibitor okadaic acid. We propose that SAC silencing in mammalian cells requires proteolysis-dependent activation of okadaic acid-resistant phosphatase(s) to reverse phosphorylations that lock the Mad2-Cdc20 complex.
详细资料
- 文献种类: Journal Article
- 期刊名称: Cell Cycle (Georgetown, Tex.)
- 期刊缩写: Cell Cycle
- 期卷页: 2010年第9卷第3期 564-569页
- 地址: CEINGE Biotecnologie Avanzate, Naples, Italy
- ISBN: 1551-4005
- 备注:PMID:20081372
学科领域生物医药 » 生物学
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