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In the wrong place at the wrong time: does cyclin mislocalization drive oncogenic transformation?

Nature Reviews Cancer volume 13, pages 201–208 (2013)Cite this article

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Abstract

Cyclin-dependent kinases (CDKs) are regulated by both cyclin abundance and cyclin localization. Increased cyclin expression in cancer was first observed two decades ago, and its role in pathogenesis has been investigated in great depth. This Opinion article focuses on the spatial deregulation of cyclin expression and its potential link to oncogenesis. It describes the contexts in which particular cyclins have been reported to be mislocalized in neoplasia, reviews the mechanisms underlying the dynamic subcellular localization of CDK–cyclin complexes in normal cells, and discusses how these controls can be disrupted in cancer. It also outlines the mechanisms by which cyclin mislocalization might disrupt cell cycle control and interfere with faithful chromosome segregation. Finally, it discusses the extent to which cyclin mislocalization might facilitate tumorigenesis in human cancer.

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Figure 1: Regulation of cell cycle processes by CDK–cyclin complexes.
Figure 2: RAN-regulated nucleocytoplasmic transport.
Figure 3: How LMW-cyclin E might interfere with mitosis.

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Acknowledgements

The author would like to thank J. Yang, H. Hochegger, R. Graeser, S. Geley and C. Ellenreider for helpful comments on an earlier version of this manuscript and also the anonymous referees for their suggestions for clarifications.

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  1. Jonathan D. Moore was previously at Vernalis (R&D), Granta Park, Great Abington, Cambridge CB21 6GB, UK. Present address: Horizon Discovery, 7100 Cambridge Research Park, Cambridge CB25 9TL, UK.

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Moore, J. In the wrong place at the wrong time: does cyclin mislocalization drive oncogenic transformation?. Nat Rev Cancer 13, 201–208 (2013). https://doi.org/10.1038/nrc3468

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