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学者姓名：王瑞文
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Abstract ：
Mitotic anaphase onset is a key cellular process tightly regulated by multiple kinases. The involvement of mitogen-activated protein kinases (MAPKs) in this process has been established in Xenopus egg extracts. However, the detailed regulatory cascade remains elusive, and it is also unknown whether the MAPK-dependent mitotic regulation is evolutionarily conserved in the single-cell eukaryotic organisms such as fission yeast (Schizosaccharomyces pombe). Here, we show that two MAPKs in S. pombe indeed act in concert to restrain anaphase-promoting complex/cyclosome (APC/C) activity upon activation of the spindle assembly checkpoint (SAC). One MAPK, Pmk1, binds to and phosphorylates Slp1Cdc20, the co-activator of APC/C. Phosphorylation of Slp1Cdc20 by Pmk1, but not by Cdk1, promotes its subsequent ubiquitylation and degradation. Intriguingly, Pmk1-mediated phosphorylation event is also required to sustain SAC under environmental stress. Thus, our study establishes a new underlying molecular mechanism of negative regulation of APC/C by MAPK upon stress stimuli, and provides a previously unappreciated framework for regulation of anaphase entry in eukaryotic cells. © 2024, Sun, Chen, Song et al.
Keyword ：
anaphase-promoting complex/cyclosome anaphase-promoting complex/cyclosome APC/C APC/C cell biology cell biology MAPK MAPK phosphorylation phosphorylation SAC SAC Slp1/Cdc20 Slp1/Cdc20 spindle assembly checkpoint spindle assembly checkpoint S. pombe S. pombe ubiquitylation ubiquitylation
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| GB/T 7714 | Sun, L. , Chen, X. , Song, C. et al. Negative regulation of APC/C activation by MAPK-mediated attenuation of Cdc20Slp1 under stress [J]. | eLife , 2024 , 13 . |
| MLA | Sun, L. et al. "Negative regulation of APC/C activation by MAPK-mediated attenuation of Cdc20Slp1 under stress" . | eLife 13 (2024) . |
| APA | Sun, L. , Chen, X. , Song, C. , Shi, W. , Liu, L. , Bai, S. et al. Negative regulation of APC/C activation by MAPK-mediated attenuation of Cdc20Slp1 under stress . | eLife , 2024 , 13 . |
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Abstract ：
The anaphase-promoting complex (APC) is a ubiquitin ligase responsible for promoting the degradation of many cell cycle regulators. One of the activators and substrate-binding proteins for the APC is Cdc20. It has been shown previously that Cdc20 can promote its own degradation by the APC in normal cycling cells mainly through a cis-degradation mode (i.e. via an intramolecular mechanism). However, how Cdc20 is degraded during the spindle assembly checkpoint (SAC) is still not fully clear. In this study, we used a dual-Cdc20 system to investigate this issue and found that the cis-degradation mode is also the major pathway responsible for Cdc20 degradation during the SAC. In addition, we found that there is an inverse relationship between APC(cdc20) activity and the transcriptional activity of the CDC20 promoter, which likely occurs through feedback regulation by APC(cdc20) substrates, such as the cyclins C1b2 and C1b5. These findings contribute to our understanding of how the inhibition of APC(cdc20) activity and enhanced Cdc20 degradation are required for proper spindle checkpoint arrest. (C) 2017 Elsevier Inc. All rights reserved.
Keyword ：
Anaphase-promoting complex Anaphase-promoting complex Cdc20 Cdc20 Post-transcriptional regulation Post-transcriptional regulation Protein degradation Protein degradation Spindle assembly checkpoint Spindle assembly checkpoint Ubiquitination Ubiquitination
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| GB/T 7714 | Wang, Ruiwen , Burton, Janet L. , Solomon, Mark J. . Transcriptional and post-transcriptional regulation of Cdc20 during the spindle assembly checkpoint in S-cerevisiae [J]. | CELLULAR SIGNALLING , 2017 , 33 : 41-48 . |
| MLA | Wang, Ruiwen et al. "Transcriptional and post-transcriptional regulation of Cdc20 during the spindle assembly checkpoint in S-cerevisiae" . | CELLULAR SIGNALLING 33 (2017) : 41-48 . |
| APA | Wang, Ruiwen , Burton, Janet L. , Solomon, Mark J. . Transcriptional and post-transcriptional regulation of Cdc20 during the spindle assembly checkpoint in S-cerevisiae . | CELLULAR SIGNALLING , 2017 , 33 , 41-48 . |
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