Protein Kinase Activity Associated with the<i>IME</i>2 Gene Product, a Meiotic Inducer in the Yeast<i>Saccharomyces cerevisiae</i>

Kominami, Kin‐ichiro; Sakata, Yushi; Sakai, Masami; Yamashita, Ichiro

doi:10.1271/bbb.57.1731

Cited by 41 publications

(43 citation statements)

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“…including the putative PEST sequence, has been implicated as a negative regulatory domain (29), consistent with a role of this domain in Ime2p stability.…”

Section: Resultssupporting

confidence: 54%

Glucose Inhibits Meiotic DNA Replication through SCF^Grr1p-Dependent Destruction of Ime2p Kinase

Purnapatre

Gray

Piccirillo

et al. 2005

Molecular and Cellular Biology

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In the budding yeast Saccharomyces cerevisiae, the cell division cycle and sporulation are mutually exclusive cell fates; glucose, which stimulates the cell division cycle, is a potent inhibitor of sporulation. Addition of moderate concentrations of glucose (0.5%) to sporulation medium did not inhibit transcription of two key activators of sporulation, IME1 and IME2, but did increase levels of Sic1p, a cyclin-dependent kinase inhibitor, resulting in a block to meiotic DNA replication. The effects of glucose on Sic1p levels and DNA replication required Grr1p, a component of the SCF Grr1p ubiquitin ligase. Sic1p is negatively regulated by Ime2p kinase, and several observations indicate that glucose inhibits meiotic DNA replication through SCF Grr1p -mediated destruction of this kinase. First, Ime2p was destabilized in the presence of glucose, and this turnover required Grr1p, a second component of SCF Grr1p , Cdc53p, and an SCF Grr1p -associated E2 enzyme, Cdc34p. Second, Ime2p-ubiquitin conjugates were detected under conditions of rapid Ime2p turnover, and conjugation of Ime2p to ubiquitin required GRR1. Third, a mutant form of Ime2p (Ime2 ⌬PEST ), in which a putative Grr1p-interacting sequence was deleted, was more stable than wild-type Ime2p. Finally, expression of the IME2⌬PEST allele bypassed the block to meiotic DNA replication caused by 0.5% glucose. In addition, Grr1p is required for later events in sporulation independently of its role in Ime2p turnover.

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“…including the putative PEST sequence, has been implicated as a negative regulatory domain (29), consistent with a role of this domain in Ime2p stability.…”

Section: Resultssupporting

confidence: 54%

Glucose Inhibits Meiotic DNA Replication through SCF^Grr1p-Dependent Destruction of Ime2p Kinase

Purnapatre

Gray

Piccirillo

et al. 2005

Molecular and Cellular Biology

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“…It also induces meiosis-speci®c genes called IME1 and IME2 (Hayashi et al, 1998b), which are speci®cally expressed early in the meiotic development and required for the entry into meiosis. IME1 activates transcription of IME2 (Smith and Mitchell, 1989;Yoshida et al, 1990), encoding the meiosis-speci®c protein kinase (Kominami et al, 1993), and both are required for premeiotic DNA synthesis and subsequent meiotic development (Mitchell, 1994). These results therefore indicate that yeast cells communicate with each other by producing carbon dioxide and elevating medium pH in order to undergo G 1 arrest and meiosis.…”

Section: Introductionmentioning

confidence: 99%

A transcriptional autoregulatory loop for KIN28–CCL1 and SRB10–SRB11, each encoding RNA polymerase II CTD kinase–cyclin pair, stimulates the meiotic development of S. cerevisiae

Ohkuni¹,

Yamashita²

2000

Yeast

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Alkalization of the medium is associated with and required for the cellular development to meiosis and sporulation in the yeast Saccharomyces cerevisiae. To elucidate the molecular mechanisms for the signi®cance of external alkalization, we isolated mutants defective in division arrest at G 1 phase under an alkaline condition. The mutants obtained had recessive alleles of SRB10 encoding the cyclin (SRB11)-dependent protein kinase that phosphorylates the CTD domain of the largest subunit of RNA polymerase II and negatively regulates the transcriptional initiation of certain genes. A Dsrb11 deletion mutant showed the same cell cycle defect. When shifted to alkali, wild-type cells decreased transcript levels of G 1 -cyclin genes (CLN1 to CLN3) and KIN28±CCL1 (encoding another CTD kinase±cyclin pair which, in contrast, stimulates the promoter clearance and transcriptional elongation in most genes), resulting in the accumulation of G 1 cells and the hypophosphorylated form of RNA polymerase II and in an increase in cell size. However, under the same conditions, a Dsrb10 mutant was defective in these events, except the downregulation of CLN1 and CLN2. The Dsrb10 mutation also in¯uenced on the transcript levels of meiosis-inducing genes called IME1 and IME2: the mutation elevated the transcript level of IME1 but reduced that of IME2, resulting in partial defects in premeiotic DNA synthesis and meiosis. Overexpression of KIN28 and CCL1 in wild-type cells impaired the alkali-induced G 1 arrest and the rate of meiosis and elevated the transcript levels of SRB11 and IME1. These results indicate that a transcriptional autoregulatory loop for KIN28±CCL1 and SRB10±SRB11 is important for G 1 arrest and meiosis. We also found that environmental conditions for meiosis ®nely regulate the transcript levels of KIN28 and CCL1, such that nitrogen starvation ®rst elevates them but subsequent alkalization of medium decreases them.

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“…In meiotic cells, motifs in the C terminus of Ime2 regulate protein stability in response to low levels of glucose (Purnapatre et al 2005;Gray et al 2008). Truncation of the carboxy-terminal third of Ime2 is hyperactivating (Kominami et al 1993;Sia and Mitchell 1995) and generates a stabilized protein that causes cells to form asci with reduced numbers of spores (dyads and triads) (Sari et al 2008). In addition, Gpa2, a Gaprotein that is activated when glucose engages the Gpr1 glucose receptor, inhibits Ime2 through its C terminus (Donzeau and Bandlow 1999).…”

mentioning

confidence: 99%

The Ras/cAMP Pathway and the CDK-Like Kinase Ime2 Regulate the MAPK Smk1 and Spore Morphogenesis in Saccharomyces cerevisiae

et al. 2009

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Meiotic development (sporulation) in the yeast Saccharomyces cerevisiae is induced by nutritional deprivation. Smk1 is a meiosis-specific MAP kinase homolog that controls spore morphogenesis after the meiotic divisions have taken place. In this study, recessive mutants that suppress the sporulation defect of a smk1-2 temperature-sensitive hypomorph were isolated. The suppressors are partial function alleles of CDC25 and CYR1, which encode the Ras GDP/GTP exchange factor and adenyl cyclase, respectively, and MDS3, which encodes a kelch-domain protein previously implicated in Ras/cAMP signaling. Deletion of PMD1, which encodes a Mds3 paralog, also suppressed the smk1-2 phenotype, and a mds3-D pmd1-D double mutant was a more potent suppressor than either single mutant. The mds3-D, pmd1-D, and mds3-D pmd1-D mutants also exhibited mitotic Ras/cAMP phenotypes in the same rank order. The effect of Ras/cAMP pathway mutations on the smk1-2 phenotype required the presence of low levels of glucose. Ime2 is a meiosis-specific CDK-like kinase that is inhibited by low levels of glucose via its carboxy-terminal regulatory domain. IME2-DC241, which removes the carboxy-terminal domain of Ime2, exacerbated the smk1-2 spore formation phenotype and prevented cyr1 mutations from suppressing smk1-2. Inhibition of Ime2 in meiotic cells shortly after Smk1 is expressed revealed that Ime2 promotes phosphorylation of Smk1's activation loop. These findings demonstrate that nutrients can negatively regulate Smk1 through the Ras/cAMP pathway and that Ime2 is a key activator of Smk1 signaling.

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Protein Kinase Activity Associated with theIME2 Gene Product, a Meiotic Inducer in the YeastSaccharomyces cerevisiae

Cited by 41 publications

References 1 publication

Glucose Inhibits Meiotic DNA Replication through SCF^Grr1p-Dependent Destruction of Ime2p Kinase

Glucose Inhibits Meiotic DNA Replication through SCF^Grr1p-Dependent Destruction of Ime2p Kinase

A transcriptional autoregulatory loop for KIN28–CCL1 and SRB10–SRB11, each encoding RNA polymerase II CTD kinase–cyclin pair, stimulates the meiotic development of S. cerevisiae

The Ras/cAMP Pathway and the CDK-Like Kinase Ime2 Regulate the MAPK Smk1 and Spore Morphogenesis in Saccharomyces cerevisiae

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Protein Kinase Activity Associated with theIME2 Gene Product, a Meiotic Inducer in the YeastSaccharomyces cerevisiae

Cited by 41 publications

References 1 publication

Glucose Inhibits Meiotic DNA Replication through SCFGrr1p-Dependent Destruction of Ime2p Kinase

Glucose Inhibits Meiotic DNA Replication through SCFGrr1p-Dependent Destruction of Ime2p Kinase

A transcriptional autoregulatory loop for KIN28–CCL1 and SRB10–SRB11, each encoding RNA polymerase II CTD kinase–cyclin pair, stimulates the meiotic development of S. cerevisiae

The Ras/cAMP Pathway and the CDK-Like Kinase Ime2 Regulate the MAPK Smk1 and Spore Morphogenesis in Saccharomyces cerevisiae

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Glucose Inhibits Meiotic DNA Replication through SCF^Grr1p-Dependent Destruction of Ime2p Kinase

Glucose Inhibits Meiotic DNA Replication through SCF^Grr1p-Dependent Destruction of Ime2p Kinase