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Published online
doi:10.1083/jcb.200812045
The Journal of Cell Biology, Vol. 185, No. 2, 193-202
The Rockefeller University Press, 0021-9525 $30.00
© Lindqvist et al.
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The decision to enter mitosis: feedback and redundancy in the mitotic entry network



Arne Lindqvist, Verónica Rodríguez-Bravo, and René H. Medema

Department of Medical Oncology, University Medical Center Utrecht, 3584 CG Utrecht, Netherlands

Correspondence to René H. Medema: r.h.medema{at}umcutrecht.nl

The decision to enter mitosis is mediated by a network of proteins that regulate activation of the cyclin B–Cdk1 complex. Within this network, several positive feedback loops can amplify cyclin B–Cdk1 activation to ensure complete commitment to a mitotic state once the decision to enter mitosis has been made. However, evidence is accumulating that several components of the feedback loops are redundant for cyclin B–Cdk1 activation during normal cell division. Nonetheless, defined feedback loops become essential to promote mitotic entry when normal cell cycle progression is perturbed. Recent data has demonstrated that at least three Plk1-dependent feedback loops exist that enhance cyclin B–Cdk1 activation at different levels. In this review, we discuss the role of various feedback loops that regulate cyclin B–Cdk1 activation under different conditions, the timing of their activation, and the possible identity of the elusive trigger that controls mitotic entry in human cells.


Abbreviations used in this paper: APC/C, anaphase-promoting complex/cyclosome; PCM, pericentriolar material; Plk1, Polo-like kinase-1.

© 2009 Lindqvist et al.
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