THR1 mediates GCN4 and CDC4 to link morphogenesis with nutrient sensing and the stress response in Candida albicans.
Int J Mol Med
; 42(6): 3193-3208, 2018 Dec.
Article
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| MEDLINE
| ID: mdl-30320368
ABSTRACT
Candida albicans (C. albicans) CDC4 (CaCDC4), encoding the Fbox protein for the substrate specificity of the Skp1cullinFbox E3 ubiquitin ligase complex, suppresses the yeasttofilament transition in C. albicans. In our previous study, Thr1 was identified as a CaCdc4associated protein using affinity purification. THR1 encodes a homoserine kinase, which is involved in the threonine biosynthesis pathway. The present study generated a strain with repressible CaCDC4 expression and continuous THR1 expression. Colony and cell morphology analyses, as well as immunoblotting, revealed that the Thr1 protein was detectable under conditions in which the expression of CaCDC4 was repressed and that the filaments resulting from the repressed expression of CaCDC4 were suppressed by the constitutive expression of THR1 in C. albicans. Additionally, by using the CaSAT1flipper method, the present study produced null mutants of THR1, GCN4, and CaCDC4. The phenotypic consequences were evaluated by growth curves, spotting assays, microscopic analysis, reverse transcriptionpolymerase chain reaction and XTTbased biofilm formation ability. The results revealed that fewer cells lacking THR1 entered the stationary phase but had no apparent morphological alteration. It was observed that the expression of THR1 was upregulated concurrently with GCN4 during nutrient depletion and that cells lacking GCN4 rescued the lethality of cells in the absence of THR1 in conditions accumulating homoserine in the threonine biosynthesis pathway. Of note, it was found that cells with either CaCDC4 or THR1 loss were sensitive to oxidative stress and osmotic stress, with those with THR1 loss being more sensitive. In addition, it was observed that cells with loss of either CaCDC4 or THR1 exhibited the ability to increase biofilm formation, with those lacking CaCDC4 exhibiting a greater extent of enhancement. It was concluded that CaCDC4 is important in the coordination of morphogenesis, nutrient sensing, and the stress response through THR1 in C. albicans.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Candida albicans
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Proteínas Fúngicas
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Nutrientes
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Fosfotransferasas (Aceptor de Grupo Alcohol)
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Proteínas F-Box
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Factores de Transcripción con Cremalleras de Leucina de Carácter Básico
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Morfogénesis
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Int J Mol Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2018
Tipo del documento:
Article