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Cdc20 的功能分析揭示了 CRY 盒在有丝分裂检验点信号中的关键作用。

Functional analysis of Cdc20 reveals a critical role of CRY box in mitotic checkpoint signaling.

机构信息

Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.

Chester Beatty Laboratories, Structural Biology Division, Institute of Cancer Research, London, UK.

出版信息

Commun Biol. 2024 Feb 9;7(1):164. doi: 10.1038/s42003-024-05859-6.

DOI:10.1038/s42003-024-05859-6
PMID:38337031
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10858191/
Abstract

Accurate mitosis is coordinated by the spindle assembly checkpoint (SAC) through the mitotic checkpoint complex (MCC), which inhibits the anaphase-promoting complex or cyclosome (APC/C). As an essential regulator, Cdc20 promotes mitotic exit through activating APC/C and monitors kinetochore-microtubule attachment through activating SAC. Cdc20 requires multiple interactions with APC/C and MCC subunits to elicit these functions. Functionally assessing these interactions within cells requires efficient depletion of endogenous Cdc20, which is highly difficult to achieve by RNA interference (RNAi). Here we generated Cdc20 RNAi-sensitive cell lines which display a penetrant metaphase arrest by a single RNAi treatment. In this null background, we accurately measured the contribution of each known motif of Cdc20 on APC/C and SAC activation. The CRY box, a previously identified degron, was found critical for SAC by promoting MCC formation and its interaction with APC/C. These data reveal additional regulation within the SAC and establish a novel method to interrogate Cdc20.

摘要

准确的有丝分裂是通过纺锤体组装检查点 (SAC) 协调的，该检查点通过有丝分裂检查点复合物 (MCC) 抑制后期促进复合物或周期蛋白体 (APC/C)。作为一个重要的调节因子，Cdc20 通过激活 APC/C 促进有丝分裂退出，并通过激活 SAC 监测着动粒微管的附着。Cdc20 需要与 APC/C 和 MCC 亚基进行多次相互作用才能发挥这些功能。在细胞内有效地评估这些相互作用需要高效地耗尽内源性 Cdc20，而这通过 RNA 干扰 (RNAi) 是很难实现的。在这里，我们生成了 Cdc20 RNAi 敏感的细胞系，通过单次 RNAi 处理即可显示出明显的中期停滞。在这个缺失背景下，我们准确地测量了 Cdc20 上每个已知基序对 APC/C 和 SAC 激活的贡献。CRY 盒是之前确定的降解基序，通过促进 MCC 的形成及其与 APC/C 的相互作用，被发现对 SAC 至关重要。这些数据揭示了 SAC 内的额外调控，并建立了一种新的方法来研究 Cdc20。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee0/10858191/78cd94adb54e/42003_2024_5859_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee0/10858191/069285c6ee0e/42003_2024_5859_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee0/10858191/2401f6403a79/42003_2024_5859_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee0/10858191/0e921db94e20/42003_2024_5859_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee0/10858191/fc923726a0bf/42003_2024_5859_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee0/10858191/78cd94adb54e/42003_2024_5859_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee0/10858191/069285c6ee0e/42003_2024_5859_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee0/10858191/2401f6403a79/42003_2024_5859_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee0/10858191/0e921db94e20/42003_2024_5859_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee0/10858191/fc923726a0bf/42003_2024_5859_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee0/10858191/78cd94adb54e/42003_2024_5859_Fig5_HTML.jpg

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