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Published online
doi:10.1083/jcb.200704117
The Journal of Cell Biology, Vol. 179, No. 4, 671-685
The Rockefeller University Press, 0021-9525 $30.00
© Skoufias et al.
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Article

Mitosis persists in the absence of Cdk1 activity when proteolysis or protein phosphatase activity is suppressed



Dimitrios A. Skoufias1, Rose-Laure Indorato1, Françoise Lacroix1, Andreas Panopoulos2, and Robert L. Margolis1,2

1 Institut de Biologie Structurale Jean-Pierre Ebel, Atomic Energy Commission/Centre National de la Recherche Scientifique, 38027 Grenoble, Cedex 1, France
2 Sidney Kimmel Cancer Center, San Diego, CA 92121

Correspondence to Dimitrios A. Skoufias: dimitrios.skoufias{at}ibs.fr; or Robert L. Margolis: rmargolis{at}skcc.org

Cellular transition to anaphase and mitotic exit has been linked to the loss of cyclin-dependent kinase 1 (Cdk1) kinase activity as a result of anaphase-promoting complex/cyclosome (APC/C)–dependent specific degradation of its cyclin B1 subunit. Cdk1 inhibition by roscovitine is known to induce premature mitotic exit, whereas inhibition of the APC/C-dependent degradation of cyclin B1 by MG132 induces mitotic arrest. In this study, we find that combining both drugs causes prolonged mitotic arrest in the absence of Cdk1 activity. Different Cdk1 and proteasome inhibitors produce similar results, indicating that the effect is not drug specific. We verify mitotic status by the retention of mitosis-specific markers and Cdk1 phosphorylation substrates, although cells can undergo late mitotic furrowing while still in mitosis. Overall, we conclude that continuous Cdk1 activity is not essential to maintain the mitotic state and that phosphatase activity directed at Cdk1 substrates is largely quiescent during mitosis. Furthermore, the degradation of a protein other than cyclin B1 is essential to activate a phosphatase that, in turn, enables mitotic exit.

Abbreviations used in this paper: APC/C, anaphase-promoting complex/cyclosome; STLC, S-trityl-L-cysteine.


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