Mechanism of Mitosis-specific Activation of MEK1

Harding, Angus; Giles, Nichole; Burgess, Andrew; Hancock, John F.; Gabrielli, Brian

doi:10.1074/jbc.m301015200

Cited by 50 publications

(49 citation statements)

References 29 publications

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“…Consequently, the decrease of ERK activity was proposed to be required for proper G 2 /M transition. 33 In our study, we observed that ERK activation persisted in cells arrested in G 2 upon p14 ARF expression (see Fig. 2).…”

Section: Discussionmentioning

confidence: 54%

p14ARF Triggers G2 Arrest Through ERK-Mediated Cdc25C Phosphorylation, Ubiquitination and Proteasomal Degradation

Eymin¹,

Claverie²,

Salon³

et al. 2006

Cell Cycle

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Section: Discussionmentioning

confidence: 54%

p14ARF Triggers G2 Arrest Through ERK-Mediated Cdc25C Phosphorylation, Ubiquitination and Proteasomal Degradation

Eymin¹,

Claverie²,

Salon³

et al. 2006

Cell Cycle

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“…These reports show that Erk1/2 had enhanced activities in the G1 through S and G2/M phases, and were activated biphasically in the G1 phase and around the M phase (Tamemoto et al, 1992). More recently, the kinase activities of Raf1, Mek1/2, and Erk1/2 were all shown to have two peaks, corresponding to the G1 phase and late G2/early mitosis, respectively (Harding et al, 2003). Simultaneous inhibition of Mek1 and 2 caused G1 arrest (Figure 7c), whereas specific depletion of Mek1 led to a G2 block (Figure 6d).…”

Section: (B) Quantification Of Resultsmentioning

confidence: 99%

“…Phosphorylated Erk also localizes to kinetochores and interacts with the motor protein CENP-E during mitosis (Zecevic et al, 1998). Most recently, it was reported that Mek1 activation during mitosis is due to a Cdc2/cyclin B-dependent proteolytic cleavage of the Nterminal Erk-binding domain (Harding et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

The MAP kinase pathway is required for entry into mitosis and cell survival

et al. 2004

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In this communication, we examined the role of the MAP kinase pathway in the G2/M phase of the cell cycle. Activation of the Plk1 and MAP kinase pathways was initially evaluated in FT210 cells, which arrest at G2 phase at the restrictive temperature (391C), due to a mutation in the cdc2 gene. Previous studies had shown that these cells enter mitosis at the nonpermissive temperature upon incubation with okadaic acid, a protein phosphatase 1 and 2A inhibitor. We show that treatment of FT210 cells at 391C with okadaic acid activated Plk1, as shown by hyperphosphorylation and elevated protein kinase activity, and also induced activation of the MAP kinase pathway. The specific Mek inhibitor PD98059 antagonized the okadaic acid-induced activation of both Plk1 and MAP kinases. This suggests that activation of the MAP kinase pathway may contribute to the okadaic acid-induced activation of Plk1 in FT210 cells at 391C. We also found that PD98059 strongly attenuated progression of HeLa cells through mitosis, and active Mek colocalizes with Plk1 at mitotic structures. To study the potential function of the MAP kinase pathway during mitosis, RNAi was used to specifically deplete five members of this pathway (Raf1, Mek1/2, Erk1/2). Each of these five protein kinases is required for cell proliferation and survival, and depletion of any of these proteins eventually leads to apoptosis. Treatment with Mek inhibitors also inhibited cell proliferation and caused apoptosis. A dramatic increase of Plk1 activities and a moderate increase of Cdc2 activities in Raf1-depleted cells indicate that Raf1-depleted cells arrest in the late G2 or M phase. Mek1 and Erk1 depletion also caused cell cycle arrest at G2, suggesting that these enzymes are required for the G2/M transition, whereas the loss of Mek2 or Erk2 caused arrest at G1.

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“…However, the evidence in support of such a role has been controversial. Although some studies have reported that ERK1/ERK2 are phosphorylated/activated during G2/M (Tamemoto et al, 1992;Edelmann et al, 1996;Wright et al, 1999;Roberts et al, 2002), others concluded that the kinases are inactivated in mitosis (Takenaka et al, 1998;Gomez-Cambronero, 1999;Hayne et al, 2000;Harding et al, 2003). These results should, however, be interpreted with caution: first, in long-term cellular synchronization studies, the synchrony of cells is not sufficient to measure accurately the level of activation of ERK1/ERK2 in each stage of the cell cycle; second, the use of microtubule-disrupting agents to isolate mitotic cells does not reflect normal progression into M phase.…”

Section: Is Erk1/2 Signaling Important For G2/m Progression and Mitosmentioning

confidence: 99%

The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition

2007

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The Ras-dependent extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase pathway plays a central role in cell proliferation control. In normal cells, sustained activation of ERK1/ERK2 is necessary for G1-to S-phase progression and is associated with induction of positive regulators of the cell cycle and inactivation of antiproliferative genes. In cells expressing activated Ras or Raf mutants, hyperactivation of the ERK1/2 pathway elicits cell cycle arrest by inducing the accumulation of cyclin-dependent kinase inhibitors. In this review, we discuss the mechanisms by which activated ERK1/ERK2 regulate growth and cell cycle progression of mammalian somatic cells. We also highlight the findings obtained from gene disruption studies.

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Mechanism of Mitosis-specific Activation of MEK1

Cited by 50 publications

References 29 publications

p14ARF Triggers G2 Arrest Through ERK-Mediated Cdc25C Phosphorylation, Ubiquitination and Proteasomal Degradation

p14ARF Triggers G2 Arrest Through ERK-Mediated Cdc25C Phosphorylation, Ubiquitination and Proteasomal Degradation

The MAP kinase pathway is required for entry into mitosis and cell survival

The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition

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