CDK1-mediated CENP-C phosphorylation modulates CENP-A binding and mitotic kinetochore localization
Journal | J. Cell Biol. 218(12):4042-4062 (2019) |
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Title | CDK1-mediated CENP-C phosphorylation modulates CENP-A binding and mitotic kinetochore localization |
Laboratory | Laboratory of Chromosome Biology〈Prof. FUKAGAWA Tatsuo〉 |
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.
Authors | Reito Watanabe (1), Masatoshi Hara (1), Ei-Ichi Okumura (2), Solène Hervé (3), Daniele Fachinetti (3), Mariko Ariyoshi (1), Tatsuo Fukagawa (1)
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PubMed | 31676716 |