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Kinases of the Aurora family are essential for the proper execution of mitosis in eukaryotes, and Aurora inhibitors are in clinical trials as anticancer drugs. We applied site-specific quantitative phosphoproteomics in conjunction with chemical inhibition of Aurora to identify mitotic Aurora substrates in fission yeast on a proteome-wide scale. We detected 8000 phosphorylation events, of which we assigned almost 6000 to a specific residue; 220 were reduced in cells exposed to the Aurora inhibitor. After controlling for unspecific effects of the inhibitor, we classified 70 sites (on 42 proteins) as probable targets of Aurora, which enabled refinement of the consensus sequence for phosphorylation by Aurora. Several of the substrate candidates were known targets of Aurora, validating the approach, but most represented newly detected Aurora substrates. The involvement of these Aurora substrates in diverse aspects of chromatin dynamics suggests that in addition to its established role in controlling chromosome compaction and attachment to the mitotic spindle, Aurora influences other aspects of chromatin architecture and function during mitosis.

This Podcast features conversations with authors of studies on cell cycle–dependent protein phosphorylation that appear in the 28 June 2011 issue of Science Signaling and the 24 June 2011 issue of Science . The senior author of the Science Signaling Research Article by Koch et al . describes her group’s identification of substrates of the kinase Aurora, which is required for mitosis throughout eukaryotes, and the implications of these findings in light of the recent development of Aurora inhibitors for treating cancer. Authors of a Research Report by Keck et al . that appears in Science discuss their phosphoproteomic analysis of centrosomal proteins that are phosphorylated during mitosis. Given the conserved nature of many of the proteins that control mitosis, both studies have important implications for understanding the dynamics of protein phosphorylation, and therefore regulation, during the cell cycle.