Counteractive Control of Polarized Morphogenesis during Mating by Mitogen-activated Protein Kinase Fus3 and G1 Cyclin-dependent Kinase

Cell polarization in response to external cues is critical to many eukaryotic cells. During pheromone-induced mating in Saccharomyces cerevisiae, the mitogen-activated protein kinase (MAPK) Fus3 induces polarization of the actin cytoskeleton toward a landmark generated by the pheromone receptor. Here, we analyze the role of Fus3 activation and cell cycle arrest in mating morphogenesis. The MAPK scaffold Ste5 is initially recruited to the plasma membrane in random patches that polarize before shmoo emergence. Polarized localization of Ste5 is important for shmooing. In fus3 mutants, Ste5 is recruited to significantly more of the plasma membrane, whereas recruitment of Bni1 formin, Cdc24 guanine exchange factor, and Ste20 p21-activated protein kinase are inhibited. In contrast, polarized recruitment still occurs in a far1 mutant that is also defective in G1 arrest. Remarkably, loss of Cln2 or Cdc28 cyclin-dependent kinase restores polarized localization of Bni1, Ste5, and Ste20 to a fus3 mutant. These and other findings suggest Fus3 induces polarized growth in G1 phase cells by down-regulating Ste5 recruitment and by inhibiting Cln/Cdc28 kinase, which prevents basal recruitment of Ste5, Cdc42-mediated asymmetry, and mating morphogenesis.

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Dual-mode regulation of the APC/C by CDK1 and MAPK controls meiosis I progression and fidelity

The Journal of Cell Biology ◽

10.1083/jcb.201305049 ◽

2014 ◽

Vol 204 (6) ◽

pp. 891-900 ◽

Cited By ~ 24

Author(s):

Ibtissem Nabti ◽

Petros Marangos ◽

Jenny Bormann ◽

Nobuaki R. Kudo ◽

John Carroll

Keyword(s):

Protein Kinase ◽

Spindle Assembly Checkpoint ◽

Mitogen Activated Protein Kinase ◽

Cyclin Dependent Kinase ◽

Anaphase Promoting Complex ◽

Female Meiosis ◽

Dual Mode ◽

Mitogen Activated Protein ◽

Meiosis I

Female meiosis is driven by the activities of two major kinases, cyclin-dependent kinase 1 (Cdk1) and mitogen-activated protein kinase (MAPK). To date, the role of MAPK in control of meiosis is thought to be restricted to maintaining metaphase II arrest through stabilizing Cdk1 activity. In this paper, we find that MAPK and Cdk1 play compensatory roles to suppress the anaphase-promoting complex/cyclosome (APC/C) activity early in prometaphase, thereby allowing accumulation of APC/C substrates essential for meiosis I. Furthermore, inhibition of MAPK around the onset of APC/C activity at the transition from meiosis I to meiosis II led to accelerated completion of meiosis I and an increase in aneuploidy at metaphase II. These effects appear to be mediated via a Cdk1/MAPK-dependent stabilization of the spindle assembly checkpoint, which when inhibited leads to increased APC/C activity. These findings demonstrate new roles for MAPK in the regulation of meiosis in mammalian oocytes.

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Mitogen-Activated Protein Kinase Hog1 Mediates Adaptation to G1 Checkpoint Arrest during Arsenite and Hyperosmotic Stress

Eukaryotic Cell ◽

10.1128/ec.00038-08 ◽

2008 ◽

Vol 7 (8) ◽

pp. 1309-1317 ◽

Cited By ~ 22

Author(s):

Iwona Migdal ◽

Yulia Ilina ◽

Markus J. Tamás ◽

Robert Wysocki

Keyword(s):

Cell Cycle ◽

Protein Kinase ◽

Cell Cycle Arrest ◽

Kinase Inhibitor ◽

Hyperosmotic Stress ◽

Mitogen Activated Protein Kinase ◽

Hog Pathway ◽

Cycle Arrest ◽

Mitogen Activated Protein

ABSTRACT Cells slow down cell cycle progression in order to adapt to unfavorable stress conditions. Yeast (Saccharomyces cerevisiae) responds to osmotic stress by triggering G1 and G2 checkpoint delays that are dependent on the mitogen-activated protein kinase (MAPK) Hog1. The high-osmolarity glycerol (HOG) pathway is also activated by arsenite, and the hog1Δ mutant is highly sensitive to arsenite, partly due to increased arsenite influx into hog1Δ cells. Yeast cell cycle regulation in response to arsenite and the role of Hog1 in this process have not yet been analyzed. Here, we found that long-term exposure to arsenite led to transient G1 and G2 delays in wild-type cells, whereas cells that lack the HOG1 gene or are defective in Hog1 kinase activity displayed persistent G1 cell cycle arrest. Elevated levels of intracellular arsenite and “cross talk” between the HOG and pheromone response pathways, observed in arsenite-treated hog1Δ cells, prolonged the G1 delay but did not cause a persistent G1 arrest. In contrast, deletion of the SIC1 gene encoding a cyclin-dependent kinase inhibitor fully suppressed the observed block of G1 exit in hog1Δ cells. Moreover, the Sic1 protein was stabilized in arsenite-treated hog1Δ cells. Interestingly, Sic1-dependent persistent G1 arrest was also observed in hog1Δ cells during hyperosmotic stress. Taken together, our data point to an important role of the Hog1 kinase in adaptation to stress-induced G1 cell cycle arrest.

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p38 Mitogen-Activated Protein Kinase- and HuR-Dependent Stabilization of p21Cip1 mRNA Mediates the G1/S Checkpoint

Molecular and Cellular Biology ◽

10.1128/mcb.00210-09 ◽

2009 ◽

Vol 29 (16) ◽

pp. 4341-4351 ◽

Cited By ~ 150

Author(s):

Vanesa Lafarga ◽

Ana Cuadrado ◽

Isabel Lopez de Silanes ◽

Rocio Bengoechea ◽

Oscar Fernandez-Capetillo ◽

...

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Protein Kinase ◽

Cell Cycle Arrest ◽

P38 Mapk ◽

Mitogen Activated Protein Kinase ◽

Γ Radiation ◽

Cycle Arrest ◽

Mitogen Activated Protein

ABSTRACT Activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in the G2/M cell cycle arrest induced by DNA damage, but little is known about the role of this signaling pathway in the G1/S transition. Upregulation of the cyclin-dependent kinase inhibitor p21Cip1 is thought to make a major contribution to the G1/S cell cycle arrest induced by γ radiation. We show here that inhibition of p38 MAPK impairs p21Cip1 accumulation and, as a result, the ability of cells to arrest in G1 in response to γ radiation. We found that p38 MAPK induces p21Cip1 mRNA stabilization, without affecting its transcription or the stability of the protein. In particular, p38 MAPK phosphorylates the mRNA binding protein HuR on Thr118, which results in cytoplasmic accumulation of HuR and its enhanced binding to the p21Cip1 mRNA. Our findings help to understand the emerging role of p38 MAPK in the cellular responses to DNA damage and reveal the existence of p53-independent networks that cooperate in modulating p21Cip1 levels at the G1/S checkpoint.

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Yeast homolog of mammalian mitogen-activated protein kinase, FUS3/DAC2 kinase, is required both for cell fusion and for G1 arrest of the cell cycle and morphological changes by the cdc37 mutation

Journal of Cell Science ◽

10.1242/jcs.107.9.2617 ◽

1994 ◽

Vol 107 (9) ◽

pp. 2617-2622 ◽

Cited By ~ 1

Author(s):

H.A. Fujimura

Keyword(s):

Protein Kinase ◽

Map Kinase ◽

Cell Fusion ◽

Morphological Changes ◽

Mitogen Activated Protein Kinase ◽

G1 Arrest ◽

Positive Role ◽

Mitogen Activated Protein ◽

Yeast Homolog

Saccharomyces cerevisiae FUS3/DAC2 protein kinase, a homolog of mammalian mitogen-activated protein (MAP) kinase, inactivates a G1 cyclin encoded by the CLN3 gene to arrest cell division in the G1 phase and activates a transcriptional factor STE12 in response to mating pheromone during sexual conjugation. To elucidate the role of the FUS3/DAC2 gene product in the mating process, I constructed and characterized dac2 cln3 double mutants. Here, I show that FUS3/DAC2 is required for completion of cell fusion even in the dac2 cln3 double mutants in which the pheromone response is restored, suggesting that FUS3/DAC2 plays a positive role in cell fusion during conjugation. In addition, the cdc dac2 and cdc37 ste double mutants were constructed and investigated for their phenotypes to clarify the relationship between FUS3/DAC2, STE7 or STE11 and CDC gene products (CDC28, 36, 37 and 39). The results indicate that FUS3/DAC2 may act upstream of CDC28 and provide evidence that the G1 arrest and morphological changes conferred by the cdc37 mutation may require FUS3/DAC2 (MAP kinase), STE7(MEK) and STE11 (MEK kinase).

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