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A more recent version of this article appeared on December 1, 2006
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Submitted on April 7, 2006
Revised on September 22, 2006
Accepted on September 29, 2006


*Division of Molecular Medicine, Wadsworth Center, New York State Department of Health, Albany, NY 12201;
Department of Biomedical Sciences, School of Public Health, and
Gen*NY*Sis Center for Excellence in Cancer Genomics, State University of New York, Albany, NY 12144; and
Marine Biology Laboratory, Woods Hole, MA 02543
Monitoring Editor: Orna Cohen-Fix
ERK1/2 activity is reported to be required in mammalian cells for timely entry into and exit from mitosis (i.e., the G2/M and M/A transitions). However, it is unclear if this involvement reflects a direct requirement for ERK1/2 activity during these transitions, or for activating gene transcription programs at earlier stages of the cell cycle. To examine these possibilities we followed live cells in which ERK1/2 activity was inhibited through late G2 and mitosis. We find that acute inhibition of ERK1/2 during late G2 and through mitosis does not affect the timing of the G2/M or M/A transitions in normal or transformed human cells, nor does it impede spindle assembly, inactivate the p38 stress-activated checkpoint during late G2 or the spindle assembly checkpoint during mitosis. Using CENP-F as a marker for progress through G2, we also show that sustained inhibition of ERK1/2 transiently delays the cell cycle in early/midG2 via a p53-dependent mechanism. Together, our data reveal that ERK1/2 activity is required in early G2 for a timely entry into mitosis but that it does not directly regulate cell-cycle progression from late G2 through mitosis in normal or transformed mammalian cells.
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