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CCDC68 通过促进 CDC20 整合到 MCC 中维持有丝分裂检查点的激活。

CCDC68 Maintains Mitotic Checkpoint Activation by Promoting CDC20 Integration into the MCC.

机构信息

Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, 100871, China.

Key Laboratory of Epigenetic Regulation and Intervention, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

出版信息

Adv Sci (Weinh). 2024 Sep;11(35):e2406009. doi: 10.1002/advs.202406009. Epub 2024 Jul 17.

DOI:10.1002/advs.202406009
PMID:39018254
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11425217/
Abstract

The spindle assembly checkpoint (SAC) ensures chromosome segregation fidelity by manipulating unattached kinetochore-dependent assembly of the mitotic checkpoint complex (MCC). The MCC binds to and inhibits the anaphase promoting complex/cyclosome (APC/C) to postpone mitotic exit. However, the mechanism by which unattached kinetochores mediate MCC formation is not yet fully understood. Here, it is shown that CCDC68 is an outer kinetochore protein that preferentially localizes to unattached kinetochores. Furthermore, CCDC68 interacts with the SAC factor CDC20 to inhibit its autoubiquitination and MCC disassembly. Therefore, CCDC68 restrains APC/C activation to ensure a robust SAC and allow sufficient time for chromosome alignment, thus ensuring chromosomal stability. Hence, the study reveals that CCDC68 is required for CDC20-dependent MCC stabilization to maintain mitotic checkpoint activation.

摘要

纺锤体组装检查点 (SAC) 通过操纵无附着的动粒依赖性有丝分裂检查点复合物 (MCC) 的组装来确保染色体分离保真度。MCC 结合并抑制后期促进复合物/周期蛋白 (APC/C) 以延迟有丝分裂退出。然而，无附着的动粒介导 MCC 形成的机制尚不完全清楚。本研究表明，CCDC68 是一种外动粒蛋白，优先定位于无附着的动粒上。此外，CCDC68 与 SAC 因子 CDC20 相互作用，抑制其自身泛素化和 MCC 解体。因此，CCDC68 抑制 APC/C 的激活以确保强大的 SAC 并为染色体对齐提供足够的时间，从而确保染色体稳定性。因此，该研究表明 CCDC68 是 CDC20 依赖性 MCC 稳定所必需的，以维持有丝分裂检查点的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/7f1656dcf632/ADVS-11-2406009-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/ad357f063520/ADVS-11-2406009-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/1b15064e401f/ADVS-11-2406009-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/7f232813078e/ADVS-11-2406009-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/897eeeb77411/ADVS-11-2406009-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/08d1b8537e00/ADVS-11-2406009-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/c0abb107ab31/ADVS-11-2406009-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/7f1656dcf632/ADVS-11-2406009-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/ad357f063520/ADVS-11-2406009-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/1b15064e401f/ADVS-11-2406009-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/7f232813078e/ADVS-11-2406009-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/897eeeb77411/ADVS-11-2406009-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/08d1b8537e00/ADVS-11-2406009-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/c0abb107ab31/ADVS-11-2406009-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d57c/11425217/7f1656dcf632/ADVS-11-2406009-g004.jpg

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