RESEARCH HIGHLIGHTS CELL CYCLE Links: Signalling crosstalk Aurora-B http://ca.expasy.org/uniprot/O70126 During mitosis, duplicated exogenous expression of either wild- INCENP chromosomes are compacted and type INCENP or INCENP that was http://ca.expasy.org/uniprot/Q9WU62 subsequently divided into two mutated at Thr59 (Thr59Ala), but daughter cells. Various mitotic not by INCENP that was mutated at Survivin kinases regulate these events, but Thr388 (Thr388Ala). This indicates http://ca.expasy.org/uniprot/O70201 how the activities of these kinases that the phosphorylation of INCENP are coordinated has been unknown. at Thr388 is important for the Cdk1 Masaki Inagaki and colleagues now recruitment of Plk1 to kinetochores. http://ca.expasy.org/uniprot/P11440 provide some insight into this regula- It also implies that the role of tory mechanism in a report in Nature INCENP in the localization of Plk1 Plk Cell Biology. is probably through direct complex http://ca.expasy.org/uniprot/Q07832 The mitotic kinase Aurora-B formation with the kinase. In addi- forms a complex with the inner cen- tion, the replacement of endogenous tromere protein (INCENP) and sur- INCENP with the Thr388Ala mutant vivin. INCENP is phosphorylated by led to a delayed progression from Aurora-B, and Inagaki and colleagues metaphase to anaphase, thereby now show that INCENP is also phos- further confirming the biological phorylated, in a mitosis-dependent significance of INCENP phosphory- manner, by cyclin-dependent kinase- lation by Cdk1. 1 (Cdk1). The authors propose that during Next, Inagaki and co-workers early mitosis INCENP is phos- found that a third mitotic kinase, phorylated by Aurora-B and Cdk1, Polo-like kinase-1 (Plk1), binds and that Plk1 is recruited to Thr388 specifically to Cdk1-phosphorylated phospho-INCENP. Plk1 is thought INCENP. This binding was dimin- to have an important role in spindle ished by mutating the Thr388, but formation by generating the micro- not the Thr59, phosphorylation site tubule forces that pull each chromo- on INCENP. The interaction between some towards the spindle pole, Plk1 and Thr388 phospho-INCENP whereas Aurora-B might function in was confirmed in vivo by the immu- ensuring the correct chromosome noprecipitation of INCENP from a attachments between kinetochores mitotic HeLa-cell extract, as Plk1 was and microtubules. Therefore, the detected, together with Aurora-B, in signalling crosstalk among Plk1, the anti-INCENP precipitate. Cdk1 and Aurora-B on INCENP, To understand the relationship and the coordinated functions of between the Aurora-B–INCENP– these kinases, might be a crucial step survivin complex and Plk1, the in chromosome segregation during authors knocked down each of the mitosis and the progression from components by RNA interference. metaphase to anaphase. They found that the depletion of Arianne Heinrichs INCENP abolished the recruit- ORIGINAL RESEARCH PAPER Goto, H. et al. ment of Plk1 to kinetochores. This Complex formation of Plk1 and INCENP required phenotype could be rescued by the for metaphase–anaphase transition. Nature Cell Biol. 8, 180–187 (2006) NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 7 | FEBRUARY 2006 | 1.