Aurora borealis wraps Plk1 and CDK together

Proper execution of mitosis requires the phosphorylation of hundreds of functional proteins by multiple protein kinases. Activation and inactivation of these kinases needs to be coordinated so that the correct order and timing of mitotic events allows faithful chromosome inheritance. The intrinsic oscillation of one of these kinases, the cyclin-dependent kinase (CDK), has been shown to be composed of a negative feedback loop and a time delay. 1 CDK first activates the anaphase-promoting complex/cyclosome (APC/C), an e3 ubiquitin ligase for mitotic cyclins, which, in turn, inactivates the CDK, forming a negative feedback loop. it takes about 15 min for the CDK to activate the APC/C by an unknown mechanism (an intrinsic time delay). in addition APC/C activation is further delayed either by the spindle assembly checkpoint in somatic cells or by a cyto-static factor (CsF) that is present in unfertilized eggs. in embryonic cycles, CDK activity oscillates as the cells enter and exit mitosis, so how are other mitotic kinases controlled during this period, while CDK activity remains high? Polo-like kinase 1 (Plk1) is one such mitotic kinase, and its activity also oscillates, peak-ing in mitosis like CDK. The protein levels of Plk1 are relatively stable in eggs and in early development stages, so its oscillating activity must be initiated by some other mechanism. This activation is performed by Aurora A (Aur A), another mitotic kinase, which phosphory-lates and activates Plk1 on entering mitosis. A recent study by Feine et al. now reveals how Plk1 activity is coordinated with CDK activity after entering mitosis via the regulated stability of a Plk1-interacting factor, Aurora borealis (Bora). 2 Bora was originally identified as a Drosophila mutant, which shows a phenotype (defective in asymmetric cell division) similar to that of a mutant of Aur A. 3 when Bora is repressed in higher vertebrates, cells form multipolar mitotic spindles, and they have aberrantly segregated chromosomes. it was also shown that Bora specifically enhances Aur A-mediated T-loop phosphorylation of Plk1 in vivo and in vitro, which is required for full activation of Plk1. 4 stability of the Bora protein is downregulated by both CDK and Plk1. initially Bora is phosphorylated at ser252 by CDK, which then permits Plk1 to phosphory-late ser497 and Thr501, which, in turn, leads to phosphorylation-dependent protein degradation by the sCF βTrCP –proteasome pathway. 5,6 Therefore, Plk1 and Bora constitute a negative feedback loop, and the question posed is how is Bora …