SUMOylated NKAP is essential for chromosome alignment by anchoring CENP-E to kinetochores.
Chromosome alignment is required for accurate chromosome segregation. Chromosome misalignment can result in genomic instability and tumorigenesis. Here, we show that NF-κB activating protein (NKAP) is critical for chromosome alignment through anchoring CENP-E to kinetochores. NKAP knockdown causes chromosome misalignment and prometaphase arrest in human cells. NKAP dynamically localizes to ... kinetochores, and is required for CENP-E kinetochore localization. NKAP is SUMOylated predominantly in mitosis and the SUMOylation is needed for NKAP to bind CENP-E. A SUMOylation-deficient mutant of NKAP cannot support the localization of CENP-E on kinetochores or proper chromosome alignment. Moreover, Bub3 recruits NKAP to stabilize the binding of CENP-E to BubR1 at kinetochores. Importantly, loss of NKAP expression causes aneuploidy in cultured cells, and is observed in human soft tissue sarcomas. These findings indicate that NKAP is a novel and key regulator of mitosis, and its dysregulation might contribute to tumorigenesis by causing chromosomal instability.
Mesh Terms:
Aneuploidy, Carcinogenesis, Cell Cycle Proteins, Chromosomal Proteins, Non-Histone, Chromosomes, Co-Repressor Proteins, Gene Expression Regulation, Neoplastic, HCT116 Cells, HeLa Cells, Humans, Kinetochores, Mitosis, Mutation, Nuclear Proteins, Poly-ADP-Ribose Binding Proteins, Protein-Serine-Threonine Kinases, Sarcoma, Sumoylation
Aneuploidy, Carcinogenesis, Cell Cycle Proteins, Chromosomal Proteins, Non-Histone, Chromosomes, Co-Repressor Proteins, Gene Expression Regulation, Neoplastic, HCT116 Cells, HeLa Cells, Humans, Kinetochores, Mitosis, Mutation, Nuclear Proteins, Poly-ADP-Ribose Binding Proteins, Protein-Serine-Threonine Kinases, Sarcoma, Sumoylation
Nat Commun
Date: Dec. 03, 2015
PubMed ID: 27694884
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