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The emerging role of APC/CCdh1 in controlling differentiation, genomic stability and tumor suppression

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Abstract

Deregulation of the G1/G0 phase of the cell cycle can lead to cancer. During G1, most cells commit alternatively to DNA replication and division, or to cell-cycle exit and differentiation. The anaphase-promoting complex or cyclosome (APC/C) activated by Cdh1 coordinately eliminates positive cell-cycle regulators as well as inhibitors of differentiation, thereby coupling cell-cycle exit and differentiation. Misregulation of Cdh1 thus has the potential to promote both cell-cycle re-entry and either perturbed differentiation or dedifferentiation. In addition, APC/CCdh1 is required to maintain genomic stability. As a result, loss of Cdh1 can contribute to tumorigenesis in the form of proliferation of poorly differentiated and genetically unstable cells.

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Acknowledgements

We thank Andrea Schmidts for helping us with Figure 2 and Monika Engelhardt for critical reading of the paper. RW thanks Roland Mertelsmann for continuous support.

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  1. Department of Hematology and Oncology, University Medical Center, Freiburg, Germany

    R Wäsch

  2. Laboratory of Yeast Molecular Genetics, The Rockefeller University, New York, NY, USA,

    J A Robbins & F R Cross

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Wäsch, R., Robbins, J. & Cross, F. The emerging role of APC/CCdh1 in controlling differentiation, genomic stability and tumor suppression. Oncogene 29, 1–10 (2010). https://doi.org/10.1038/onc.2009.325

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