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

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

Molecular Biology of the Cell ◽

10.1091/mbc.e07-08-0757 ◽

2008 ◽

Vol 19 (4) ◽

pp. 1739-1752 ◽

Cited By ~ 20

Author(s):

Lu Yu ◽

Maosong Qi ◽

Mark A. Sheff ◽

Elaine A. Elion

Keyword(s):

Plasma Membrane ◽

Protein Kinase ◽

Cell Polarization ◽

Mitogen Activated Protein Kinase ◽

G1 Arrest ◽

Cyclin Dependent Kinase ◽

Cycle Arrest ◽

Mitogen Activated Protein ◽

Cdc28 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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Isc10, an Inhibitor That Links the Anaphase-Promoting Complex to a Meiosis-Specific Mitogen-Activated Protein Kinase

Molecular and Cellular Biology ◽

10.1128/mcb.00097-20 ◽

2020 ◽

Vol 40 (16) ◽

Author(s):

Abhimannyu Rimal ◽

Zeal P. Kamdar ◽

Chong Wai Tio ◽

Edward Winter

Keyword(s):

Protein Kinase ◽

Ubiquitin Ligase ◽

Double Mutant ◽

Ternary Complex ◽

E3 Ubiquitin Ligase ◽

Mitogen Activated Protein Kinase ◽

Dependent Manner ◽

Anaphase Promoting Complex ◽

Mitogen Activated Protein ◽

Meiosis I

ABSTRACT Smk1 is a meiosis-specific mitogen-activated protein kinase (MAPK) in yeast that controls spore differentiation. It is activated by a MAPK binding protein, Ssp2, upon completion of the meiotic divisions. The activation of Smk1 by Ssp2 is positively regulated by a meiosis-specific coactivator of the anaphase promoting complex (APC/C) E3 ubiquitin ligase, Ama1. Here, we identify Isc10 as an inhibitor that links APC/CAma1 to Smk1 activation. Isc10 and Smk1 form an inhibited complex during meiosis I (MI). Ssp2 is produced later in the program, and it forms a ternary complex with Isc10 and Smk1 during MII that is poised for activation. Upon completion of MII, Isc10 is ubiquitylated and degraded in an AMA1-dependent manner, thereby triggering the activation of Smk1 by Ssp2. Mutations that caused Ssp2 to be produced before MII, or isc10Δ mutations, modestly reduced the efficiency of spore differentiation whereas spores were nearly absent in the double mutant. These findings define a pathway that couples spore differentiation to the G0-like phase of the cell cycle.

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P1154 Inhibition of p38 mitogen-activated protein kinase prevents endothelial dysfunction in chronic heart failure: role of vascular superoxide anion production

European Heart Journal ◽

10.1016/s0195-668x(03)94446-0 ◽

2003 ◽

Vol 24 (5) ◽

pp. 213

Author(s):

J WIDDER

Keyword(s):

Heart Failure ◽

Protein Kinase ◽

Chronic Heart Failure ◽

Endothelial Dysfunction ◽

Superoxide Anion ◽

Mitogen Activated Protein Kinase ◽

Superoxide Anion Production ◽

Anion Production ◽

Mitogen Activated Protein

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Role of p38 Mitogen-activated Protein Kinase and Caspases in UV-B–induced Apoptosis of Murine Peritoneal Macrophages¶

Photochemistry and Photobiology ◽

10.1562/0031-8655(2004)79<48:ropmpk>2.0.co;2 ◽

2004 ◽

Vol 79 (1) ◽

pp. 48 ◽

Cited By ~ 2

Author(s):

Gautam Sethi ◽

Ajit Sodhi

Keyword(s):

Protein Kinase ◽

Peritoneal Macrophages ◽

Mitogen Activated Protein Kinase ◽

Mitogen Activated Protein ◽

Murine Peritoneal Macrophages ◽

Induced Apoptosis

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Faculty Opinions recommendation of Peroxisome proliferator activator receptor gamma coactivator-1 expression is reduced in obesity: potential pathogenic role of saturated fatty acids and p38 mitogen-activated protein kinase activation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1084943.537900 ◽

2007 ◽

Author(s):

Mark Hargreaves

Keyword(s):

Fatty Acids ◽

Protein Kinase ◽

Saturated Fatty Acids ◽

Mitogen Activated Protein Kinase ◽

Peroxisome Proliferator ◽

Pathogenic Role ◽

Kinase Activation ◽

Protein Kinase Activation ◽

Mitogen Activated Protein

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The Role of Cdh1p in Maintaining Genomic Stability in Budding Yeast

Genetics ◽

10.1093/genetics/165.2.489 ◽

2003 ◽

Vol 165 (2) ◽

pp. 489-503 ◽

Cited By ~ 1

Author(s):

Karen E Ross ◽

Orna Cohen-Fix

Keyword(s):

Cell Cycle ◽

Chromosome Segregation ◽

Spindle Assembly Checkpoint ◽

Chromosome Loss ◽

Cyclin Dependent Kinase ◽

Anaphase Promoting Complex ◽

Growth Defects ◽

Genes Encoding ◽

Specificity Factor

Abstract Cdh1p, a substrate specificity factor for the cell cycle-regulated ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C), promotes exit from mitosis by directing the degradation of a number of proteins, including the mitotic cyclins. Here we present evidence that Cdh1p activity at the M/G1 transition is important not only for mitotic exit but also for high-fidelity chromosome segregation in the subsequent cell cycle. CDH1 showed genetic interactions with MAD2 and PDS1, genes encoding components of the mitotic spindle assembly checkpoint that acts at metaphase to prevent premature chromosome segregation. Unlike cdh1Δ and mad2Δ single mutants, the mad2Δ cdh1Δ double mutant grew slowly and exhibited high rates of chromosome and plasmid loss. Simultaneous deletion of PDS1 and CDH1 caused extensive chromosome missegregation and cell death. Our data suggest that at least part of the chromosome loss can be attributed to kinetochore/spindle problems. Our data further suggest that Cdh1p and Sic1p, a Cdc28p/Clb inhibitor, have overlapping as well as nonoverlapping roles in ensuring proper chromosome segregation. The severe growth defects of both mad2Δ cdh1Δ and pds1Δ cdh1Δ strains were rescued by overexpressing Swe1p, a G2/M inhibitor of the cyclin-dependent kinase, Cdc28p/Clb. We propose that the failure to degrade cyclins at the end of mitosis leaves cdh1Δ mutant strains with abnormal Cdc28p/Clb activity that interferes with proper chromosome segregation.

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