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Securin and B-cyclin/CDK are the only essential targets of the APC

Nature Cell Biology volume 5, pages 1090–1094 (2003)Cite this article

Abstract

The anaphase-promoting complex/cyclosome (APC) is a highly conserved ubiquitin ligase that controls passage through the cell cycle by targeting many proteins for proteolysis1. The complex is composed of at least thirteen core subunits2, eight of which are essential1,3,4,5, and two activating subunits, Cdc20 (essential) and Cdh1/Hct1 (non-essential)6,7. Previously, it was not known which APC targets are sufficient to explain the essential nature of the complex. Here, we show that each of the eight normally essential APC subunits is rendered non-essential ('bypass-suppressed') by the simultaneous removal/inhibition of the APC substrates securin (Pds1) and B-type cyclin/CDK (Clb/CDK). In strains lacking the APC, levels of Clb2 and Clb3 remain constant, but Clb/CDK activity oscillates as cells cycle. This suggests that in the absence of B-type cyclin destruction, oscillation of the Clb/CDK-inhibitor Sic1 is sufficient to trigger the feedback loops necessary for the bi-stable nature of Clb/CDK activity. These results strongly suggest that securin and B-type cyclin/CDK activity are the only obligatory targets of the APC in Saccharomyces cerevisiae.

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Figure 1: Deletion of APC11 is bypass-suppressed by pds1Δ clb5Δ SIC110X.
Figure 2: Suppressed APC deletion strains cycle despite stabilization of Clb2 and other APC substrates.
Figure 3: Strains lacking Cdc27 retain limited APC activity.
Figure 4: A model of a minimal cell cycle in Apc− cells.

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Acknowledgements

We thank S. Biggins, O. Cohen-Fix, J. Diffley, D. Kellogg, J. Li, D. Morgan, A. Murray, A. Page, D. Pellman, A. Rudner, and M. Tyers for antibodies, plasmids and strains, A. Sil for help with centrifugal elutriation, D. Kellogg for his suggestion of Swe1 as a potential APC substrate, and S. Biggins, C. Carroll, D. Kellogg, J. Li, D. Morgan, A. Rudner, and all members of the lab for helpful discussions and critical reading of the manuscript. This work was supported by a Cancer Research Coordinating Committee (CRCC) grant and National Institutes of Health grant GM59691-01. B.R.T. is supported by a Howard Hughes Medical Institute pre-graduate fellowship.

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  1. S-332 Department of Biochemistry and Biophysics University of California, Cancer Research Institute, San Francisco, 2340 Sutter Street, San Francisco, 94115, CA, USA

    Brian R. Thornton & David P. Toczyski

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Correspondence to David P. Toczyski.

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Thornton, B., Toczyski, D. Securin and B-cyclin/CDK are the only essential targets of the APC. Nat Cell Biol 5, 1090–1094 (2003). https://doi.org/10.1038/ncb1066

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