SALLY WHEATLEY AND WILLIAM C. EARNSHAW

In animal cells cytokinesis begins shortly after the separation of sister chromatids. Although many genes have been implicated either in cytokinesis or chromosome segregation, the exact mechanism by which these processes are regulated is unknown. Three recent papers, by Adams et al. (Curr. Biol. 10, 1075–1078; 2000), Severson et al. (Curr. Biol. 10, 1162–1171; 2000) and Kaitna et al. ( Curr. Biol. 10, 1172–1181; 2000), have shed light on the precise functions of Aurora-related kinases, inner-cetromere protein (INCENP) and the mitotic-like kinesin (MLK) MKLP1/ZEN-4 in both chromosome segregation and cytokinesis.

Using Xenopus laevis eggs, Adams and colleagues demonstrated that Xenopus INCENP is stockpiled in an exclusive complex with Aurora-B/X-AIRK2 (Xenopus Aurora-related serine–threonine kinase) and that the two proteins co-localize during anaphase (picture shows INCENP in red and Aurora-B/AIRK2 in green). The authors demonstrated an in vitro interaction between INCENP and Aurora-B/AIRK2, as previously shown in budding yeast. In human cells, transient expression of dominant negative INCENP prevented correct localization of the endogenous protein during metaphase and led to defects in Aurora-B/X-AIRK2 localization.

In an independent study, Kaitna and colleagues identified two Caenorhabditis elegans proteins, ICP-1 and ICP-2, that share homology with vertebrate INCENP, and confirmed the above results. Using RNA interefence (RNAi) in C. elegans embryos, they showed that both ICP-1 and Aurora-B/AIR-2 are essential for chromosome segregation and cytokinesis. They went on to demonstrate that C. elegans Aurora-B/AIR-2 and ICP-1 can also interact in vitro , and that their mammalian homologues interact in vivo. The authors also showed that localization of AIR-2 in C. elegans relies on INCENP.

On the basis of these two studies, it seems that INCENP localizes AIR-2 to chromosomes during metaphase, and that it also has a role in cytokinesis that is directly linked to its ability to correctly localize Aurora-B/AIR-2.

In C. elegans embryos with conditional mutations in Aurora-B/AIR-2, Severson and colleagues showed that the MLK, CeMKLP1/ZEN-4, was not localized to the spindle interzone as compared with wild-type embryos, preventing cytokinesis from proceeding. Not unexpectedly, Severson and colleagues observed an in vitro interaction between Aurora-B/AIR-2 and CeMLKP1/ZEN-4.

From all these findings it seems that Aurora-B/AIR-2 does have two separate functions — one in DNA segregation and one in cytokinesis. How Aurora-B/AIR-2 regulates chromosome segregation, along with INCENP, is unknown. However, these important studies have begun to unravel the role of Aurora-related kinases during cell division, and we await with interest the identification of the precise mechanisms that control their action.