Plk1 puts a (Has)pin on the mitotic histone code

Abstract

Haspin is an atypical mitotic kinase that phosphorylates histone H3 on threonine 3 (H3T3), which is required to target Aurora B to centromeres. However, how Haspin is activated upon mitotic entry remained unknown. Two independent studies, published in Molecular Cell and in this issue of EMBO reports by Ghenoiu et al and Zhou et al, respectively, now show that Plk1 is responsible for Haspin activation as a H3T3 kinase. These results shed light on the spatiotemporal regulation of Aurora B to ensure mitotic fidelity.

Figure 1

Cell cycle regulation of Haspin, the H3T3 kinase. Haspin is an atypical kinase that is kept inactive during interphase through the interaction of a specific region in its N-terminus—enriched in basic amino acids and known as Haspin basic inhibitory segment (HBIS)—with its kinase domain. Upon mitotic entry, the Cdk1/cyclin B complex phosphorylates a specific threonine residue (T128) on human Haspin (T206 in Xenopus), generating a polo-box domain recognition site on Haspin. During prophase, Plk1 heavily phosphorylates the N-terminus of Haspin, leading to its activation and resulting in the phosphorylation of the threonine 3 on histone H3 tail on threonine 3 (H3T3). This specific histone post-translation modification is necessary for the recruitment of the chromosomal passenger complex (CPC) to centromeres. During prometaphase, Haspin is also phosphorylated by the catalytic subunit of CPC—the Aurora B kinase—which ensures that H3T3 phosphorylation at centromeres is maintained.