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Sci. Signal., 28 June 2011
Vol. 4, Issue 179, p. rs6
[DOI: 10.1126/scisignal.2001588]
RESEARCH RESOURCES
Mitotic Substrates of the Kinase Aurora with Roles in Chromatin Regulation Identified Through Quantitative Phosphoproteomics of Fission Yeast
André Koch1,
Karsten Krug2,
Stuart Pengelley2*,
Boris Macek2, and
Silke Hauf1
1 Friedrich Miescher Laboratory of the Max Planck Society, 72076 Tuebingen, Germany. 2 Proteome Center Tuebingen, University of Tuebingen, 72076 Tuebingen, Germany.
Abstract:
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.
To whom correspondence should be addressed. E-mail: boris.macek{at}uni-tuebingen.de (B.M.); silke.hauf{at}tuebingen.mpg.de (S.H.)
Citation: A. Koch, K. Krug, S. Pengelley, B. Macek, S. Hauf, Mitotic Substrates of the Kinase Aurora with Roles in Chromatin Regulation Identified Through Quantitative Phosphoproteomics of Fission Yeast. Sci. Signal.4, rs6 (2011).
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, and
Silke Hauf1
