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 localizationof 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-Anucleosomal complexes containCENP-Candphosphobinding 14-3-3 proteins. In contrast, mitotic nucleosomal complexes carryingnonphosphorylatable CENP-A-S7Acontainedonly lowlevels of CENP-C and no detectable 14-3-3 proteins. Direct interactions betweenthephosphorylatedformofCENP- Aand14-3-3proteinsaswell 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.
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Publication status||Published - 21 May 2013|
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