TY - JOUR
T1 - Phosphorylation of the CENP-A amino-terminus in mitotic centromeric chromatin is required for kinetochore function
AU - Goutte-Gattat, Damien
AU - Shuaib, Muhammad
AU - Ouararhni, Khalid
AU - Gautier, Thierry
AU - Skoufias, Dimitrios A.
AU - Hamiche, Ali
AU - Dimitrov, Stefan
PY - 2013/5/21
Y1 - 2013/5/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84878140645&partnerID=8YFLogxK
U2 - 10.1073/pnas.1302955110
DO - 10.1073/pnas.1302955110
M3 - Article
C2 - 23657009
AN - SCOPUS:84878140645
SN - 0027-8424
VL - 110
SP - 8579
EP - 8584
JO - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
IS - 21
ER -