TY - JOUR
T1 - Dynamic phosphorylation of HP1α regulates mitotic progression in human cells
AU - Chakraborty, Arindam
AU - Prasanth, Kannanganattu V.
AU - Prasanth, Supriya G.
N1 - Funding Information:
We thank members of the Prasanth laboratory for discussions and suggestions. We also thank Drs P. Chambon, J. Chen, W. Dai, M. Dundr, B. Hemmings, Y. Hiraoka, J. Nakayama, H. Yu, P. Silver, D. Spector and B. Stillman for providing reagents and suggestions. We thank Drs D. Rivier and S. Ceman for critical reading of the paper. This work was supported by NIH (1RO1GM088252) award to K.V.P. and NSF (0843604), NSF career (1243372) and NIH (1RO1GM099669) awards to S.G.P.
PY - 2014/3/12
Y1 - 2014/3/12
N2 - 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.
AB - 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.
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U2 - 10.1038/ncomms4445
DO - 10.1038/ncomms4445
M3 - Article
C2 - 24619172
AN - SCOPUS:84896279040
SN - 2041-1723
VL - 5
JO - Nature communications
JF - Nature communications
M1 - 3445
ER -