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.
CDK1-mediated CENP-C phosphorylation modulates CENP-A binding and mitotic kinetochore localization
- Views Icon Views
- Share Icon Share
- Tools Icon Tools
- Search Site
Reito Watanabe, Masatoshi Hara, Ei-ichi Okumura, Solène Hervé, Daniele Fachinetti, Mariko Ariyoshi, Tatsuo Fukagawa; CDK1-mediated CENP-C phosphorylation modulates CENP-A binding and mitotic kinetochore localization. J Cell Biol 2 December 2019; 218 (12): 4042–4062. doi: https://doi.org/10.1083/jcb.201907006
Download citation file: