title: Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B.
abstract: A hallmark of mitosis is the appearance of high levels of histone phosphorylation, yet the roles of these modifications remain largely unknown. Here, we demonstrate that histone H3 phosphorylated at threonine 3 is directly recognized by an evolutionarily conserved binding pocket in the BIR domain of Survivin, which is a member of the chromosomal passenger complex (CPC). This binding mediates recruitment of the CPC to chromosomes and the resulting activation of its kinase subunit Aurora B. Consistently, modulation of the kinase activity of Haspin, which phosphorylates H3T3, leads to defects in the Aurora B-dependent processes of spindle assembly and inhibition of nuclear reformation. These findings establish a direct cellular role for mitotic histone H3T3 phosphorylation, which is read and translated by the CPC to ensure accurate cell division.
authors: Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10065, USA. akelly@rockefeller.edu
authors: Alexander E
authors: AE
authors: Kelly
authors: Cristina
authors: C
authors: Ghenoiu
authors: John Z
authors: JZ
authors: Xue
authors: Christian
authors: C
authors: Zierhut
authors: Hiroshi
authors: H
authors: Kimura
authors: Hironori
authors: H
authors: Funabiki
mesh_terms: D000818:Animals; D064127:Aurora Kinases; D002455:Cell Division; D002503:Centromere / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism*; D004789:Enzyme Activation; D006657:Histones / Q000378:metabolism*; D008938:Mitosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D000077022:Survivin; D013912:Threonine / Q000378:metabolism; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; C506222:INCENP protein, Xenopus; D000077022:Survivin; D029867:Xenopus Proteins; C472712:birc5.2 protein, Xenopus; C488974:cdca9 protein, Xenopus; C553144:survivin protein, Xenopus laevis; D013912:Threonine; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C553143:haspin protein, Xenopus laevis