Mps1 promotes rapid centromere accumulation of Aurora B.
Aurora B localization to mitotic centromeres, which is required for proper chromosome alignment during mitosis, relies on Haspin-dependent histone H3 phosphorylation and on Bub1-dependent histone H2A phosphorylation--which interacts with Borealin through a Shugoshin (Sgo) intermediate. We demonstrate that Mps1 stimulates the latter recruitment axis. Mps1 activity enhances H2A-T120ph and is critical for Sgo1 recruitment to centromeres, thereby promoting Aurora B centromere recruitment in early mitosis. Importantly, chromosome biorientation defects caused by Mps1 inhibition are improved by restoring Aurora B centromere recruitment. As Mps1 kinetochore localization reciprocally depends on Aurora B, we propose that this Aurora B-Mps1 recruitment circuitry cooperates with the Aurora B-Haspin feedback loop to ensure rapid centromere accumulation of Aurora B at the onset of mitosis.
Department of Medical Oncology, University Medical Center Utrecht, Universiteitsweg 100, STR 2.129, 3584 CG Utrecht, The Netherlands.
Maike S
MS
van der Waal
Adrian T
AT
Saurin
Martijn J M
MJ
Vromans
Mathijs
M
Vleugel
Claudia
C
Wurzenberger
Daniel W
DW
Gerlich
René H
RH
Medema
Geert J P L
GJ
Kops
Susanne M A
SM
Lens
D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D018386:Kinetochores / Q000201:enzymology*; D008938:Mitosis; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
D018797:Cell Cycle Proteins; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C496644:SGO1 protein, human; D011505:Protein-Tyrosine Kinases; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; C530656:HASPIN protein, human; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human