Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activating phosphorylation of cyclin-dependent protein kinases (CDKs) is necessary for their kinase activity and cell cycle progression. This phosphorylation is carried out by the Cdk-activating kinase (CAK); in contrast, little is known about the corresponding protein phosphatase. We show that type 2C protein phosphatases (PP2Cs) are responsible for this dephosphorylation of Cdc28p, the major budding yeast CDK. Two yeast PP2Cs, Ptc2p and Ptc3p, display Cdc28p phosphatase activity in vitro and in vivo, and account for approximately 90% of Cdc28p phosphatase activity in yeast extracts. Overexpression of PTC2 or PTC3 results in synthetic lethality in strains temperature-sensitive for yeast CAK1, and disruptions of PTC2 and PTC3 suppress the growth defect of a cak1 mutant. Furthermore, PP2C-like enzymes are the predominant phosphatases toward human Cdk2 in HeLa cell extracts, indicating that the substrate specificity of PP2Cs toward CDKs is evolutionarily conserved.
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PMID:Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases. 1058 2

RAD53 encodes a conserved protein kinase that acts as a central transducer in the DNA damage and the DNA replication checkpoint pathways in Saccharomyces cerevisiae. To identify new elements of these pathways acting with or downstream of RAD53, we searched for genes whose overexpression suppressed the toxicity of a dominant-lethal form of RAD53 and identified PTC2, which encodes a protein phosphatase of the PP2C family. PTC2 overexpression induces hypersensitivity to genotoxic agents in wild-type cells and is lethal to rad53, mec1, and dun1 mutants with low ribonucleotide reductase activity. Deleting PTC2 specifically suppresses the hydroxyurea hypersensitivity of mec1 mutants and the lethality of mec1Delta. PTC2 is thus implicated in one or several functions related to RAD53, MEC1, and the DNA checkpoint pathways.
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PMID:Involvement of the PP2C-like phosphatase Ptc2p in the DNA checkpoint pathways of Saccharomyces cerevisiae. 1074 50

Candida albicans is the most common cause of invasive fungal infections in humans. Its ability to sense and adapt to changing carbon dioxide levels is crucial for its pathogenesis. Carbon dioxide promotes hyphal development. The hypha-specific transcription factor Ume6 is rapidly degraded in air, but is stable under physiological CO₂ and hypoxia to sustain hyphal elongation. Here, we show that Ume6 stability is regulated by two parallel E3 ubiquitin ligases, SCF^Grr1 and Ubr1, in response to CO₂ and O₂, respectively. To uncover the CO₂ signaling pathway that regulates Ume6 stability, we performed genetic screens for mutants unable to respond to CO₂ for sustained filamentation. We find that the type 2C protein phosphatase Ptc2 is specifically required for CO₂-induced stabilization of Ume6 and hyphal elongation. In contrast, the cyclin-dependent kinase Ssn3 is found to be required for Ume6 phosphorylation and degradation in atmospheric CO₂ Furthermore, we find that Ssn3 is dephosphorylated in 5% CO₂ in a Ptc2-dependent manner, whereas deletion of PTC2 has no effect on Ssn3 phosphorylation in air. Our study uncovers the Ptc2-Ssn3 axis as a new CO₂ signaling pathway that controls hyphal elongation by regulating Ume6 stability in C. albicans IMPORTANCE The capacity to sense and adapt to changing carbon dioxide levels is crucial for all organisms. In fungi, CO₂ is a key determinant involved in fundamental biological processes, including growth, morphology, and virulence. In the pathogenic fungus Candida albicans, high CO₂ is directly sensed by adenylyl cyclase to promote hyphal growth. However, little is known about the mechanism by which hyphal development is maintained in response to physiological levels of CO₂ Here we report that a signal transduction system mediated by a phosphatase-kinase pair controls CO₂-responsive Ume6 phosphorylation and stability that in turn dictate hyphal elongation. Our results unravel a new regulatory mechanism of CO₂ signaling in fungi.
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PMID:CO₂ Signaling through the Ptc2-Ssn3 Axis Governs Sustained Hyphal Development of Candida albicans by Reducing Ume6 Phosphorylation and Degradation. 3064 54

In the pathogenic fungus Candida albicans, phosphoregulation of the checkpoint kinase Rad53 plays a crucial role in the filamentous growth response to genotoxic stresses. The protein phosphatase 4 (PP4) complex, containing Pph3 and either Psy2 or Psy4, is proved to play a critical role in Rad53 dephosphorylation. In previous studies, we characterized CaPtc2 (the ortholog of both Ptc2 and Ptc3 in Saccharomyces cerevisiae) as a potential DNA-damage-related protein phosphatase. In this study, we checked the genetic interaction of PTC2 with the PP4 complex in the DNA damage response pathway. The results suggest that Ptc2 shows a negative genetic interaction with Pph3, but positive genetic interaction with either Psy2 or Psy4 in response to genotoxic stress. Deletion of PTC2 alone resulted in no significant change in cell virulence, but double deletion of PTC2 PPH3 significantly decreased virulence, while double deletions of either PTC2 PSY2 or PTC2 PSY4 caused virulence levels similar to that shown by PSY2 or PSY4 single-gene deletion cells. Taken together, we propose that Ptc2 in C. albicans plays a compensatory role for Pph3 but is dependent on Psy2 and Psy4 in regulation of DNA damage and cell virulence.
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PMID:Genetic interaction between Ptc2 and protein phosphatase 4 (PP4) in the regulation of DNA damage response and virulence in Candida albicans. 3164 92

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