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Survivin Reads Phosphorylated Histone H3 Threonine 3 to Activate the Mitotic Kinase Aurora B
Alexander E. Kelly,1,*,
Cristina Ghenoiu,1,2,*
John Z. Xue,1
Christian Zierhut,1
Hiroshi Kimura,3
Hironori Funabiki1,
Abstract:
A hallmark of mitosis is the appearance of high levels of histonephosphorylation, yet the roles of these modifications remainlargely unknown. Here, we demonstrate that histone H3 phosphorylatedat threonine 3 is directly recognized by an evolutionarily conservedbinding pocket in the BIR domain of Survivin, which is a memberof the chromosomal passenger complex (CPC). This binding mediatesrecruitment of the CPC to chromosomes and the resulting activationof its kinase subunit Aurora B. Consistently, modulation ofthe kinase activity of Haspin, which phosphorylates H3T3, leadsto defects in the Aurora B–dependent processes of spindleassembly and inhibition of nuclear reformation. These findingsestablish a direct cellular role for mitotic histone H3T3 phosphorylation,which is read and translated by the CPC to ensure accurate celldivision.
1 Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10065, USA. 2 Weill Cornell Graduate School of Biomedical Sciences, Department of Molecular Biology, Cornell Medical School, New York, NY 10021, USA. 3 School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: funabih{at}rockefeller.edu (H.F.); akelly{at}rockefeller.edu (A.E.K.)
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