Open Access

THR1 mediates GCN4 and CDC4 to link morphogenesis with nutrient sensing and the stress response in Candida albicans

  • Authors:
    • Yuan‑Ti Lee
    • Yi‑Ya Fang
    • Yu Wen Sun
    • Hsiao‑Chi Hsu
    • Shan‑Mei Weng
    • Tzu‑Ling Tseng
    • Ting‑Hui Lin
    • Jia‑Ching Shieh
  • View Affiliations

  • Published online on: October 12, 2018     https://doi.org/10.3892/ijmm.2018.3930
  • Pages: 3193-3208
  • Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Candida albicans (C. albicans) CDC4 (CaCDC4), encoding the F‑box protein for the substrate specificity of the Skp1‑cullin‑F‑box E3 ubiquitin ligase complex, suppresses the yeast‑to‑filament transition in C. albicans. In our previous study, Thr1 was identified as a CaCdc4‑associated 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 CaSAT1‑flipper 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 transcription‑polymerase chain reaction and XTT‑based 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.
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December-2018
Volume 42 Issue 6

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Lee YT, Fang YY, Sun YW, Hsu HC, Weng SM, Tseng TL, Lin TH and Shieh JC: THR1 mediates GCN4 and CDC4 to link morphogenesis with nutrient sensing and the stress response in Candida albicans. Int J Mol Med 42: 3193-3208, 2018
APA
Lee, Y., Fang, Y., Sun, Y.W., Hsu, H., Weng, S., Tseng, T. ... Shieh, J. (2018). THR1 mediates GCN4 and CDC4 to link morphogenesis with nutrient sensing and the stress response in Candida albicans. International Journal of Molecular Medicine, 42, 3193-3208. https://doi.org/10.3892/ijmm.2018.3930
MLA
Lee, Y., Fang, Y., Sun, Y. W., Hsu, H., Weng, S., Tseng, T., Lin, T., Shieh, J."THR1 mediates GCN4 and CDC4 to link morphogenesis with nutrient sensing and the stress response in Candida albicans". International Journal of Molecular Medicine 42.6 (2018): 3193-3208.
Chicago
Lee, Y., Fang, Y., Sun, Y. W., Hsu, H., Weng, S., Tseng, T., Lin, T., Shieh, J."THR1 mediates GCN4 and CDC4 to link morphogenesis with nutrient sensing and the stress response in Candida albicans". International Journal of Molecular Medicine 42, no. 6 (2018): 3193-3208. https://doi.org/10.3892/ijmm.2018.3930