Positive control of sporulation-specific genes by the IME1 and IME2 products in Saccharomyces cerevisiae.

Mitchell, Aaron P.; Driscoll, S E; Smith, Harold E.

doi:10.1128/mcb.10.5.2104

Cited by 125 publications

(171 citation statements)

References 26 publications

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“…3A); expression of HOPl preceded expression of SPSl by ~2 hr, and expres sion of DITl began 2 hr after the SPSl gene had been turned on. This sequential pattern of gene expression was consistent with previous observations (Briza et al 1990b;Mitchell et al 1990;Smith et al 1990). …”

Section: Spsl Is Expressed As Meiosis Is Nearing Completionsupporting

confidence: 81%

Mutation of the SPS1-encoded protein kinase of Saccharomyces cerevisiae leads to defects in transcription and morphology during spore formation.

Friesen¹,

Lunz²,

Doyle³

et al. 1994

Genes Dev.

116

132

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During spoiulation of Saccharomyces cerevisiae, meiosis is followed by encapsulation of haploid nuclei within multilayered spore walls. Completion of the late events of the sporulation program requires the SPSl gene. This developmentally regulated gene, which is expressed as cells are nearing the end of meiosis, encodes a protein with homology to serine/threonine protein kinases. The catalytic domain of Spsl is 44% identical to the kinase domain of yeast Ste20, a protein involved in the pheromone-induced signal transduction pathway. Cells of a MATa./MATa. spsl/spsl strain arrest after meiosis and fail to activate genes that are normally expressed at a late time of sporulation. The mutant cells do not form refractile spores as assessed by phase-contrast microscopy and do not display the natural fluorescence and ether resistance that is characteristic of mature spores. Examination by electron microscopy reveals, however, that prospore-like compartments form in some of the mutant cells. These immature spores lack the cross-linked surface layer that surrounds wild-type spores and are more variable in size and number than are the spores of wild-type cells. Despite their inability to complete spore formation, spsl-arrested cells are able to resume mitotic growth on transfer to rich medium, generating haploid progeny. Our results suggest that the developmentally regulated Spsl kinase is required for normal progression of transcriptional, biochemical, and morphological events during the later portion of the sporulation program.

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Section: Spsl Is Expressed As Meiosis Is Nearing Completionsupporting

confidence: 81%

Mutation of the SPS1-encoded protein kinase of Saccharomyces cerevisiae leads to defects in transcription and morphology during spore formation.

Friesen¹,

Lunz²,

Doyle³

et al. 1994

Genes Dev.

116

132

View full text Add to dashboard Cite

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“…They contained the complete ORFs from the G 1 cyclin gene CLN2, the B-type cyclin genes CLB1, CLB3, and CLB5, and a truncated CLB1 cDNA lacking the N-terminal 120 aa, CLB1-dN. In addition, we identified plasmids containing the entire ORF of IME2, encoding a meiosis-specific protein kinase with sequence similarities to CDKs (30,31). Immunoblotting showed that the expression of these cDNAs caused the accumulation of Clb2-lacZ protein in G 1 -arrested cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…It is unknown whether Ime2 also is permanently unstable during meiosis or whether it then gets periodically stabilized. Stabilization could be a mechanism to allow efficient accumulation of Ime2 in early meiosis, in addition to the transcriptional induction of the IME2 gene (31,43).…”

Section: Is Ime2 Activity Regulated By Its Stabilitymentioning

confidence: 99%

Inhibition of APC-mediated proteolysis by the meiosis-specific protein kinase Ime2

Bolte

Steigemann²,

Braus³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Proteolysis triggered by the anaphase-promoting complex (APC) is needed for sister chromatid separation and the exit from mitosis. APC is a ubiquitin ligase whose activity is tightly controlled during the cell cycle. To identify factors involved in the regulation of APC-mediated proteolysis, a Saccharomyces cerevisiae GAL-cDNA library was screened for genes whose overexpression prevented degradation of an APC target protein, the mitotic cyclin Clb2. Genes encoding G1, S, and mitotic cyclins were identified, consistent with previous data showing that the cyclin-dependent kinase Cdk1 associated with different cyclins is a key factor for inhibiting APC Cdh1 activity from late-G1 phase until mitosis. In addition, the meiosis-specific protein kinase Ime2 was identified as a negative regulator of APC-mediated proteolysis. Ectopic expression of IME2 in G1 arrested cells inhibited the degradation of mitotic cyclins and of other APC substrates. IME2 expression resulted in the phosphorylation of Cdh1 in G1 cells, indicating that Ime2 and Cdk1 regulate APC Cdh1 in a similar manner. The expression of IME2 in cycling cells inhibited bud formation and caused cells to arrest in mitosis. We show further that Ime2 itself is an unstable protein whose proteolysis occurs independently of the APC and SCF (Skp1͞ Cdc53͞F-box) ubiquitin ligases. Our findings suggest that Ime2 represents an unstable, meiosis-specific regulator of APC Cdh1 .C rucial processes in the cell cycle, such as initiation of DNA replication, separation of sister chromatids, and exit from mitosis, depend on proteolytic degradation of critical regulatory proteins (1-3). Ubiquitin ligases play essential roles in these degradation processes. These enzymes catalyze the formation of chains of ubiquitin on their substrates, thereby targeting them for degradation by the 26S proteasome (4). The anaphasepromoting complex (APC), also known as cyclosome, is a multisubunit complex acting as ubiquitin ligase (5, 6). APC is essential for mitosis, and its activity is tightly cell cycle-regulated. Its activation at the metaphase͞anaphase transition requires its association with the activator protein Cdc20. APC Cdc20 triggers proteolytic degradation of the securin Pds1. Upon Pds1 proteolysis, the separase Esp1 is liberated, cleaves the cohesin subunit Scc1, and thereby triggers sister chromatid separation (7). APC Cdc20 also initiates proteolysis of the S phase cyclin Clb5 and a fraction of mitotic cyclins (8-10). APC Cdc20 activation is inhibited by the spindle assembly checkpoint, which prevents sister chromatid separation upon defects in the mitotic spindle or in the attachment of kinetochores (11).Cdh1 (also termed Hct1) is related to Cdc20 and is needed for complete degradation of mitotic cyclins (12, 13). Cdh1's potential to associate with the APC is controlled by phosphorylation (14, 15). The cyclin-dependent kinase Cdk1 phosphorylates Cdh1, thereby preventing its interaction with APC. A Cdk1-antagonizing phosphatase, Cdc14, is kept inactive in the nucleolus for most of the...

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“…In the earliest stages of meiosis Ime2 positively regulates Ime1-dependent transcription of early meiosis-specific genes (14). Ime2 also appears to promote early gene transcription in an Ime1-independent fashion.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 98%

Arg-Pro-X-Ser/Thr Is a Consensus Phosphoacceptor Sequence for the Meiosis-Specific Ime2 Protein Kinase in Saccharomyces cerevisiae

et al. 2006

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Ime2 is a meiosis-specific protein kinase in Saccharomyces cerevisiae that is functionally related to cyclin-dependent kinase. Although Ime2 regulates multiple steps in meiosis, only a few of its substrates have been identified. Here we show that Ime2 phosphorylates Sum1, a repressor of meiotic gene transcription, on Thr-306. Ime2 protein kinase assays on Sum1 mutants and synthetic peptides define a consensus motif Arg-Pro-X-Ser/Thr that is required for efficient phosphorylation by Ime2. The carboxyl residue adjacent to the phosphoacceptor (+1 position) also influences the efficiency of Ime2 phosphorylation with alanine being a preferred residue. This information has predictive value in identifying new potential Ime2 targets as shown by the ability of Ime2 to phosphorylate Sgs1 and Gip1 in vitro, and could be important in differentiating mitotic and meiotic regulatory pathways. Keywordsyeast; meiosis; protein kinase; Ime2; Sum1; consensus phosphorylation site Meiosis is a specialized form of cell division that produces the haploid cells required for sexual reproduction. It is characterized by DNA replication, high levels of genetic recombination, and two sequential rounds of chromosome segregation. These processes require the choreographed expression of meiosis-specific genes in a transcriptional cascade (11,31). In the budding yeast Saccharomyces cerevisiae, meiosis is induced by nutrient depletion and is coupled to spore formation. Starvation for key nutrients induces expression of the early gene transcriptional activator Ime1 (12). One of the genes activated by Ime1 encodes Ime2, a serine/threonine kinase that is functionally related to the Cdc28 cyclin-dependent kinase (CDK) and which shows similarity to the CMGC-group of protein kinases (10). Ime2 is required for critical events in meiosis, including the replication of DNA, the regulation of meiotic gene expression, and the meiotic divisions. † This work was supported by grants from the National Institutes of Health to Andrew Vershon (GM 58762) and Edward Winter GM (GM061817).*>To whom correspondence should be addressed: 233 South 10th St., Philadelphia, PA 19107. Phone:(215) 923-9162. E-mail: edward.winter@jefferson.edu.. Π These authors contributed equally to this work. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptThe role that Ime2 plays in regulating meiotic S phase is related to that of Cdc28 in triggering Sphase in mitosis. In both mitosis and meiosis the G 1 -S transition is prohibited by the Clb5,6/ Cdc28 inhibitor Sic1 (24). Entry into S phase is delayed until Sic1 is phosphorylated, a reaction catalyzed in mitosis by Cdc28 in complex with the G 1 -phase cyclins Cln1 and Cln2 (15,30). In meiosis, Ime2 is required for Sic1 degradation and DNA replication (7). Others have recently demonstrated that Ime2 directly phosphorylates multiple sites in Sic1 in vitro. This is insufficient to trigger meiotic Sic1 destruction, however, suggesting that Ime2 does not simply replace the function of Cln1,2-/Cdc28 in meiosis to ...

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Positive control of sporulation-specific genes by the IME1 and IME2 products in Saccharomyces cerevisiae.

Cited by 125 publications

References 26 publications

Mutation of the SPS1-encoded protein kinase of Saccharomyces cerevisiae leads to defects in transcription and morphology during spore formation.

Mutation of the SPS1-encoded protein kinase of Saccharomyces cerevisiae leads to defects in transcription and morphology during spore formation.

Inhibition of APC-mediated proteolysis by the meiosis-specific protein kinase Ime2

Arg-Pro-X-Ser/Thr Is a Consensus Phosphoacceptor Sequence for the Meiosis-Specific Ime2 Protein Kinase in Saccharomyces cerevisiae

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