title: Basal aurora kinase B activity is sufficient for histone H3 phosphorylation in prophase.
abstract: Histone H3 phosphorylation is the hallmark of mitosis deposited by aurora kinase B. Benzo[e]pyridoindoles are a family of potent, broad, ATP-competitive aurora kinase inhibitors. However, benzo[e]pyridoindole C4 only inhibits histone H3 phosphorylation in prophase but not in metaphase. Under the C4 treatment, the cells enter into mitosis with dephosphorylated histone H3, assemble chromosomes normally and progress to metaphase, and then to anaphase. C4 also induces lagging chromosome in anaphase but we demonstrated that these chromosome compaction defects are not related to the absence of H3 phosphorylation in prophase. As a result of C4 action, mitosis lasts longer and the cell cycle is slowed down. We reproduced the mitotic defects with reduced concentrations of potent pan aurora kinase as well as with a specific aurora B ATP-competitive inhibitor; we therefore propose that histone H3 phosphorylation and anaphase chromosome compaction involve the basal activity of aurora kinase B. Our data suggest that aurora kinase B is progressively activated at mitosis entry and at anaphase onset. The full activation of aurora kinase B by its partners, in prometaphase, induces a shift in the catalytic domain of aurora B that modifies its affinity for ATP. These waves of activation/deactivation of aurora B correspond to different conformations of the chromosomal complex revealed by FRAP. The presence of lagging chromosomes may have deleterious consequences on the daughter cells and, unfortunately, the situation may be encountered in patients receiving treatment with aurora kinase inhibitors.
authors.affiliation: CRI INSERM UJF U823, Institut Albert Bonniot, 38 706 La Tronche Cedex , France ; Permanent address: Da Nang University of Technology, Da Nang City, Vietnam.
authors.forename: Ly-Thuy-Tram
authors.initials: LT
authors.lastname: Le
authors.forename: Hong-Lien
authors.initials: HL
authors.lastname: Vu
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Nguyen
authors.forename: Annie
authors.initials: A
authors.lastname: Molla
keywords: Aurora kinase; Cancer; Chromosomal passenger complex; Chromosome compaction; Histone H3 phosphorylation; Kinase inhibitors; Survivin