Actin dysfunction activates ERK1/2 and delays entry into mitosis in mammalian cells

Kyunghee Lee, Kiwon Song

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Investigations of actin function during the cell cycle have focused primarily on cytokinesis. Here, we describe the role of actin at the entry into mitosis in primary mammalian cells. Depolymerization of actin with cytochalasin D or inhibition of myosin ATPase with butanedione-2-monoxime (BDM) at G 2 blocked the mitotic spindle formation and central positioning of the nucleus in synchronized MEF and IMR90 cells. Time-lapse microscopy confirmed that these treatments inhibit both spindle formation and separation of duplicated centrosomes to the opposite poles. Concurrent with actin dysfunction, activation of Cdc2 and nuclear localization of cyclin B1 were delayed. Furthermore, cyclin A degradation that is necessary for nuclear envelope breakdown (NEBD) in early mitosis was deferred, supporting the conclusion that mitotic onset was delayed. The activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) was sustained in these cells, and the use of a specific ERK inhibitor or a dominant negative form of ERK2 abrogated this delay of entry into mitosis. This delay of mitotic entry and the sustained ERK1/2 activity by actin dysfunction was observed only in primary cells and not in transformed cancer cell lines. These observations demonstrate that an intact actin cytoskeleton is necessary for entry into mitosis and that ERK1/2 is involved in monitoring actin dysfunction to control the onset of mitosis, suggesting the presence of an actin checkpoint at the G2/M transition in primary mammalian cells.

Original languageEnglish
Pages (from-to)1487-1495
Number of pages9
JournalCell Cycle
Volume6
Issue number12
Publication statusPublished - 2007 Jun 15

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Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Mitosis
Actins
Cyclin B1
Cytochalasin D
Cyclin A
Centrosome
Transformed Cell Line
Spindle Apparatus
Cytokinesis
Nuclear Envelope
Myosins
Actin Cytoskeleton
Microscopy
Cell Cycle
Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

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abstract = "Investigations of actin function during the cell cycle have focused primarily on cytokinesis. Here, we describe the role of actin at the entry into mitosis in primary mammalian cells. Depolymerization of actin with cytochalasin D or inhibition of myosin ATPase with butanedione-2-monoxime (BDM) at G 2 blocked the mitotic spindle formation and central positioning of the nucleus in synchronized MEF and IMR90 cells. Time-lapse microscopy confirmed that these treatments inhibit both spindle formation and separation of duplicated centrosomes to the opposite poles. Concurrent with actin dysfunction, activation of Cdc2 and nuclear localization of cyclin B1 were delayed. Furthermore, cyclin A degradation that is necessary for nuclear envelope breakdown (NEBD) in early mitosis was deferred, supporting the conclusion that mitotic onset was delayed. The activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) was sustained in these cells, and the use of a specific ERK inhibitor or a dominant negative form of ERK2 abrogated this delay of entry into mitosis. This delay of mitotic entry and the sustained ERK1/2 activity by actin dysfunction was observed only in primary cells and not in transformed cancer cell lines. These observations demonstrate that an intact actin cytoskeleton is necessary for entry into mitosis and that ERK1/2 is involved in monitoring actin dysfunction to control the onset of mitosis, suggesting the presence of an actin checkpoint at the G2/M transition in primary mammalian cells.",
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Actin dysfunction activates ERK1/2 and delays entry into mitosis in mammalian cells. / Lee, Kyunghee; Song, Kiwon.

In: Cell Cycle, Vol. 6, No. 12, 15.06.2007, p. 1487-1495.

Research output: Contribution to journalArticle

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