Graduate School of Frontier Biosciences, Osaka University

Japanese

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

Journal J Cell Biol, in press (2019)
Authors Watanabe R (1), Hara M (1), Okumura EI (2), Hervé S (3), Fachinetti D (3), Ariyoshi M (1), Fukagawa T (1)
  1. Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan
  2. Laboratory of Cell and Developmental Biology, Graduate School of Bioscience, Tokyo Institute of Technology, Yokohama, Japan
  3. Institute Curie, Paris Sciences et Lettres Research University, Centre national de la recherche scientifique, UMR 144, Paris, France
Title CDK1-mediated CENP-C phosphorylation modulates CENP-A binding and mitotic kinetochore localization
PubMed 31676716
Laboratory Laboratory of Chromosome Biology 〈Prof. Fukagawa〉
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.