Isolation of a Schizosaccharomyces pombe Gene Which in High Copy Confers Resistance to the Nucleoside Analogue 5‐Azacytidine

Platt, Georgina M.; Price, C P

doi:10.1002/(sici)1097-0061(199704)13:5<463::aid-yea89>3.3.co;2-2

Cited by 4 publications

(5 citation statements)

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“…The second category of genes are those that have genomic DNA methylation, but are not endogenously silenced (such as EHsp100, HSP70, 687.m00016, 3.m00674, 160.m00098, 26.m00304) [18]. Whether the second category of genes (except for EHsp100 which is sensitive to 5-AzaC treatment) are more resistant to 5-AzaC [37] or are those in which the methylation profile is not due to methyltransferases but instead due to other factors, such as dsRNA-directed methylation [38], is not clear at present.…”

Section: Resultsmentioning

confidence: 99%

Growth of the protozoan parasite Entamoeba histolytica in 5-azacytidine has limited effects on parasite gene expression

et al. 2007

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Background: In higher eukaryotes DNA methylation regulates important biological functions including silencing of gene expression and protection from adverse effects of retrotransposons. In the protozoan parasite Entamoeba histolytica, a DNA methyltransferase has been identified and treatment with 5-azacytidine (5-AzaC), a potent inhibitor of DNA methyltransferase, has been reported to attenuate parasite virulence. However, the overall extent of DNA methylation and its subsequent effects on global gene expression in this parasite are currently unknown.

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Section: Resultsmentioning

confidence: 99%

Growth of the protozoan parasite Entamoeba histolytica in 5-azacytidine has limited effects on parasite gene expression

et al. 2007

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“…S1 in the supplemental material). The azr1 ϩ gene was originally isolated as a multicopy suppressor of the 5-azacytidine sensitivity of G 2 checkpoint-and DNA repair-deficient S. pombe strains (69), but the phosphatase activity of Azr1 has never been demonstrated. The expression of the CaPTC7 gene is developmentally regulated at both the transcriptional and protein levels during serum-induced morphogenesis, suggesting that CaPtc7 might be an important regulator of morphogenesis of this organism.…”

Section: Downloaded Frommentioning

confidence: 99%

Type 2C Protein Phosphatases in Fungi

2011

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Type 2C Ser/Thr phosphatases are a remarkable class of protein phosphatases, which are conserved in eukaryotes and involved in a large variety of functional processes. Unlike in other Ser/Thr phosphatases, the catalytic polypeptide is not usually associated with regulatory subunits, and functional specificity is achieved by encoding multiple isoforms. For fungi, most information comes from the study of type 2C protein phosphatase (PP2C) enzymes in Saccharomyces cerevisiae, where seven PP2C-encoding genes (PTC1 to -7) with diverse functions can be found. More recently, data on several Candida albicans PP2C proteins became available, suggesting that some of them can be involved in virulence. In this work we review the available literature on fungal PP2Cs and explore sequence databases to provide a comprehensive overview of these enzymes in fungi.Reversible phosphorylation of proteins is a major mechanism regulating many biological processes such as metabolism, gene transcription, or cell cycle. It is an extremely common event in signal transduction, and it is considered the main mechanism of posttranslational modification leading, for instance, to a change in enzyme activity. The phosphorylation state of a protein results from the balance of protein kinases and protein phosphatases activities. Alterations in the phosphorylation state of proteins are a cause of various diseases, such as cancer, diabetes, rheumatoid arthritis, or hypertension. The importance of this regulatory mechanism is evident when it is considered that it affects around 30% of the proteome of Saccharomyces cerevisiae (72) and that the number of genes encoding phosphatases and kinases represents 2 to 4% of all genes in a typical eukaryotic genome (60).Most phosphorylation events in eukaryotes involve transfer of phosphate to Ser and Thr residues. Removal of this phosphate is catalyzed by Ser/Thr protein phosphatases. Members of this large family of enzymes were initially classified, using enzymological criteria, as type 1 (PP1) and type 2 (PP2) phosphatases. PP2 enzymes were subsequently divided into three groups on the basis of the requirements for metal ions: 2A (not requiring metal ions), 2B (activated by calcium), and 2C (Mg 2ϩ dependent) (10). The molecular cloning of a number of cDNAs and genes from diverse organisms allowed the establishment of three major subfamilies: PPP (phosphoprotein phosphatases), including type 1, 2A, and 2B phosphatases, among others; PPM (metal-dependent protein phosphatases), including type 2C enzymes (PP2C), which are the subject of this review; and the catalytically Asp-based subfamily, represented by HAD and FCP/SCP (see reference 89 for a review).Although PP2C proteins are distantly related in primary sequence to PPP enzymes, their tridimensional structure and catalytic mechanisms appear to be quite similar. Type 2C phosphatases are widely represented in bacteria, fungi, plants, insects, and mammals (83), suggesting that they are involved in key cellular processes, such as proliferation, metabolism, and cell...

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“…In the presence of 0.12 M MgCl 2 , the ⌬ppb1 cells failed to grow, whereas wild-type cells grew well. Notably, recent studies revealed that ptc1 ϩ , ptc2 ϩ , and ptc3 ϩ are implicated in the negative regulation of the stress-activated Wis1-Spc1-Atf1 MAPK signaling, whereas ptc4 ϩ is reported to play a role in vacuole fusion (Gaits and Russell, 1999), and azr1 ϩ plays a role in 5-azacytidine sensitivity (Platt and Price, 1997). The ptc3 ϩ encodes a member of the PP2C that is highly similar to the budding yeast PTC3 and human isoforms of PP2C.…”

Section: Isolation Of the Ptc3 ؉ Gene As A Multicopy Suppressor Of Camentioning

confidence: 99%

Atf1 Is a Target of the Mitogen-activated Protein Kinase Pmk1 and Regulates Cell Integrity in Fission Yeast

Takada

Nishimura

Asayama

et al. 2007

MBoC

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In fission yeast, knockout of the calcineurin gene resulted in hypersensitivity to Cl(-), and the overexpression of pmp1(+) encoding a dual-specificity phosphatase for Pmk1 mitogen-activated protein kinase (MAPK) or the knockout of the components of the Pmk1 pathway complemented the Cl(-) hypersensitivity of calcineurin deletion. Here, we showed that the overexpression of ptc1(+) and ptc3(+), both encoding type 2C protein phosphatase (PP2C), previously known to inactivate the Wis1-Spc1-Atf1 stress-activated MAPK signaling pathway, suppressed the Cl(-) hypersensitivity of calcineurin deletion. We also demonstrated that the mRNA levels of these two PP2Cs and pyp2(+), another negative regulator of Spc1, are dependent on Pmk1. Notably, the deletion of Atf1, but not that of Spc1, displayed hypersensitivity to the cell wall-damaging agents and also suppressed the Cl(-) hypersensitivity of calcineurin deletion, both of which are characteristic phenotypes shared by the mutation of the components of the Pmk1 MAPK pathway. Moreover, micafungin treatment induced Pmk1 hyperactivation that resulted in Atf1 hyperphosphorylation. Together, our results suggest that PP2C is involved in a negative feedback loop of the Pmk1 signaling, and results also demonstrate that Atf1 is a key component of the cell integrity signaling downstream of Pmk1 MAPK.

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Isolation of a Schizosaccharomyces pombe Gene Which in High Copy Confers Resistance to the Nucleoside Analogue 5‐Azacytidine

Cited by 4 publications

References 8 publications

Growth of the protozoan parasite Entamoeba histolytica in 5-azacytidine has limited effects on parasite gene expression

Growth of the protozoan parasite Entamoeba histolytica in 5-azacytidine has limited effects on parasite gene expression

Type 2C Protein Phosphatases in Fungi

Atf1 Is a Target of the Mitogen-activated Protein Kinase Pmk1 and Regulates Cell Integrity in Fission Yeast

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