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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 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/mid-G2 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.

molecular biology of the cell

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

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

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