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CDK1 介导的 CENP-C 磷酸化调节 CENP-A 结合和有丝分裂动粒定位。

CDK1-mediated CENP-C phosphorylation modulates CENP-A binding and mitotic kinetochore localization.

机构信息

Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.

Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan

出版信息

J Cell Biol. 2019 Dec 2;218(12):4042-4062. doi: 10.1083/jcb.201907006. Epub 2019 Nov 1.

DOI:10.1083/jcb.201907006
PMID:31676716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6891089/
Abstract

The kinetochore is essential for faithful chromosome segregation during mitosis. To form a functional kinetochore, constitutive centromere-associated network (CCAN) proteins are assembled on the centromere chromatin that contains the centromere-specific histone CENP-A. CENP-C, a CCAN protein, directly interacts with the CENP-A nucleosome to nucleate the kinetochore structure. As CENP-C is a hub protein for kinetochore assembly, it is critical to address how the CENP-A-CENP-C interaction is regulated during cell cycle progression. To address this question, we investigated the CENP-C C-terminal region, including a conserved CENP-A-binding motif, in both chicken and human cells and found that CDK1-mediated phosphorylation of CENP-C facilitates its binding to CENP-A in vitro and in vivo. We observed that CENP-A binding is involved in CENP-C kinetochore localization during mitosis. We also demonstrate that the CENP-A-CENP-C interaction is critical for long-term viability in human RPE-1 cells. These results provide deeper insights into protein-interaction network plasticity in centromere proteins during cell cycle progression.

摘要

着丝粒对于有丝分裂过程中染色体的正确分离至关重要。为了形成一个功能性的着丝粒，组成性着丝粒相关网络（CCAN）蛋白被组装在包含着丝粒特异性组蛋白 CENP-A 的着丝粒染色质上。CENP-C 是一种 CCAN 蛋白，它直接与 CENP-A 核小体相互作用，从而引发着丝粒结构的形成。由于 CENP-C 是着丝粒组装的枢纽蛋白，因此解决 CENP-A-CENP-C 相互作用在细胞周期进展过程中如何受到调控的问题至关重要。为了解决这个问题，我们研究了鸡和人细胞中的 CENP-C C 端区域，包括一个保守的 CENP-A 结合基序，发现 CDK1 介导的 CENP-C 磷酸化促进了其在体外和体内与 CENP-A 的结合。我们观察到 CENP-A 结合参与了有丝分裂过程中 CENP-C 着丝粒的定位。我们还证明了 CENP-A-CENP-C 相互作用对于人 RPE-1 细胞的长期存活至关重要。这些结果深入了解了细胞周期进展过程中着丝粒蛋白中蛋白质相互作用网络的可塑性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/ab5b8f4cbe53/JCB_201907006_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/647fa54da48a/JCB_201907006_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/638071f72a2a/JCB_201907006_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/4d4fa99cf2b5/JCB_201907006_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/1d0ce1f3cefa/JCB_201907006_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/dbf0b10d5b19/JCB_201907006_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/b0d4a82c9b92/JCB_201907006_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/93817cb44601/JCB_201907006_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/ab5b8f4cbe53/JCB_201907006_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/647fa54da48a/JCB_201907006_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/638071f72a2a/JCB_201907006_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/4d4fa99cf2b5/JCB_201907006_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/1d0ce1f3cefa/JCB_201907006_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/dbf0b10d5b19/JCB_201907006_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/b0d4a82c9b92/JCB_201907006_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/93817cb44601/JCB_201907006_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e76e/6891089/ab5b8f4cbe53/JCB_201907006_Fig8.jpg

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