Dynamic phosphorylation of HP1? regulates mitotic progression in human cells.

ABSTRACT: Heterochromatin protein 1? (HP1?), a key player in the establishment and maintenance of higher-order chromatin regulates key cellular processes, including metaphase chromatid cohesion and centromere organization. However, how HP1? controls these processes is not well understood. Here we demonstrate that post-translational modifications of HP1? dictate its mitotic functions. HP1? is constitutively phosphorylated within its amino terminus, whereas phosphorylation within the hinge domain occurs preferentially at G2/M phase of the cell cycle. The hinge-phosphorylated form of HP1? specifically localizes to kinetochores during early mitosis and this phosphorylation mediated by NDR1 kinase is required for mitotic progression and for Sgo1 binding to mitotic centromeres. Cells lacking NDR kinase show loss of mitosis-specific phosphorylation of HP1? leading to prometaphase arrest. Our results reveal that NDR kinase catalyses the hinge-specific phosphorylation of human HP1? during G2/M in vivo and this orchestrates accurate chromosome alignment and mitotic progression.

SUBMITTER: Chakraborty A 

PROVIDER: S-EPMC3982596 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature