Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function. - Université Grenoble Alpes
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2013

Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function.

Muhammad Shuaib
  • Fonction : Auteur
Khalid Ouararhni
  • Fonction : Auteur
Thierry Gautier
Ali Hamiche
Stefan Dimitrov

Résumé

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.

Dates et versions

hal-01322371 , version 1 (27-05-2016)

Identifiants

Citer

Damien Goutte-Gattat, Muhammad Shuaib, Khalid Ouararhni, Thierry Gautier, Dimitrios Skoufias, et al.. Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function.. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110 (21), pp.8579-84. ⟨hal-01322371⟩
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