Extracellular Signal-regulated Kinase 1/2 Activity Is Not Required in Mammalian Cells during Late G2for Timely Entry into or Exit from Mitosis

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Abstract
Extracellular signal-regulated kinase (ERK)1/2 activity is reported to be required in mammalian cells for timely entry into and exit from mitosis (i.e., the G2-mitosis [G2/M] and metaphase-anaphase [M/A] transitions). However, it is unclear whether 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 G2and mitosis. We find that acute inhibition of ERK1/2 during late G2and 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 G2or 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/mid-G2via a p53-dependent mechanism. Together, our data reveal that ERK1/2 activity is required in early G2for a timely entry into mitosis but that it does not directly regulate cell cycle progression from late G2through mitosis in normal or transformed mammalian cells.