title: Dynamic phosphorylation of HP1α regulates mitotic progression in human cells.
abstract: Heterochromatin protein 1α (HP1α), 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 HP1α controls these processes is not well understood. Here we demonstrate that post-translational modifications of HP1α dictate its mitotic functions. HP1α 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 HP1α 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 HP1α leading to prometaphase arrest. Our results reveal that NDR kinase catalyses the hinge-specific phosphorylation of human HP1α during G2/M in vivo and this orchestrates accurate chromosome alignment and mitotic progression.
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601S Goodwin Avenue, Urbana, Illinois 61801, USA.
authors.forename: Arindam
authors.initials: A
authors.lastname: Chakraborty
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601S Goodwin Avenue, Urbana, Illinois 61801, USA.
authors.forename: Kannanganattu V
authors.initials: KV
authors.lastname: Prasanth
authors.affiliation: Department of Cell and Developmental Biology, University of Illinois at Urbana-Champaign, 601S Goodwin Avenue, Urbana, Illinois 61801, USA.
authors.forename: Supriya G
authors.initials: SG
authors.lastname: Prasanth
mesh_terms: D002460:Cell Line; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation
chemical_list: C000715594:CBX5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D000090266:Chromobox Protein Homolog 5