Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis.
Aurora B is a component of the chromosomal passenger complex (CPC) required for correct spindle-kinetochore attachments during chromosome segregation and for cytokinesis. The chromatin factors that recruit the CPC to centromeres are unknown, however. Here we show that phosphorylation of histone H3 threonine 3 (H3T3ph) by Haspin is necessary for CPC accumulation at centromeres and that the CPC subunit Survivin binds directly to H3T3ph. A nonbinding Survivin-D70A/D71A mutant does not support centromeric CPC concentration, and both Haspin depletion and Survivin-D70A/D71A mutation diminish centromere localization of the kinesin MCAK and the mitotic checkpoint response to taxol. Survivin-D70A/D71A mutation and microinjection of H3T3ph-specific antibody both compromise centromeric Aurora B functions but do not prevent cytokinesis. Therefore, H3T3ph generated by Haspin positions the CPC at centromeres to regulate selected targets of Aurora B during mitosis.
Wang
Fangwei
F
Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School, Smith Building, 1 Jimmy Fund Way, Boston, MA 02115, USA.
Dai
Jun
J
Daum
John R
JR
Niedzialkowska
Ewa
E
Banerjee
Budhaditya
B
Stukenberg
P Todd
PT
Gorbsky
Gary J
GJ
Higgins
Jonathan M G
JM
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002503:Centromere / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D009154:Mutation; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011994:Recombinant Proteins / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D000077022:Survivin; D013552:Swine; D013912:Threonine / Q000378:metabolism; D014981:Xenopus
C107489:BIRC5 protein, human; C490157:CDCA8 protein, human; D018797:Cell Cycle Proteins; D002843:Chromatin; D006657:Histones; D051034:Inhibitor of Apoptosis Proteins; D047908:Intracellular Signaling Peptides and Proteins; C091489:KIF2C protein, human; D008869:Microtubule-Associated Proteins; D011994:Recombinant Proteins; D000077022:Survivin; D013912:Threonine; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; C530656:HASPIN protein, human; D017346:Protein Serine-Threonine Kinases; D016547:Kinesins