title: Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function.
abstract: The role of the mitotic phosphorylation of the amino (NH2) terminus of Centromere Protein A (CENP-A), the histone variant epigenetic centromeric marker, remains elusive. Here, we show that the NH2 terminus of human CENP-A is essential for mitotic progression and that localization of CENP-C, another key centromeric protein, requires only phosphorylation of the CENP-A NH2 terminus, and is independent of the CENP-A NH2 terminus length and amino acid sequence. Mitotic CENP-A nucleosomal complexes contain CENP-C and phosphobinding 14-3-3 proteins. In contrast, mitotic nucleosomal complexes carrying nonphosphorylatable CENP-A-S7A contained only low levels of CENP-C and no detectable 14-3-3 proteins. Direct interactions between the phosphorylated form of CENP-A and 14-3-3 proteins as well as between 14-3-3 proteins and CENP-C were demonstrated. Taken together, our results reveal that 14-3-3 proteins could act as specific mitotic "bridges," linking phosphorylated CENP-A and CENP-C, which are necessary for the platform function of CENP-A centromeric chromatin in the assembly and maintenance of active kinetochores.
authors: Institut National de la Santé et de la Recherche Médicale, Université Joseph-Fourier-Grenoble 1, Institut Albert Bonniot, Unité 823, 38042 Grenoble Cedex 9, France.
authors: Damien
authors: D
authors: Goutte-Gattat
authors: Muhammad
authors: M
authors: Shuaib
authors: Khalid
authors: K
authors: Ouararhni
authors: Thierry
authors: T
authors: Gautier
authors: Dimitrios A
authors: DA
authors: Skoufias
authors: Ali
authors: A
authors: Hamiche
authors: Stefan
authors: S
authors: Dimitrov
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D020125:Mutation, Missense; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary
chemical_list: D048948:14-3-3 Proteins; D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D009707:Nucleosomes; C060905:centromere protein C
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