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The protein kinases family in fungi: adaptability, virulence and conservation between species

Summary

Protein kinases are cellular ‘switches’ that help fungi survive harsh conditions by regulating how cells make proteins and adapt to stress. A particularly important kinase called GCN2 acts as a sensor that detects when fungi lack amino acids, triggering a survival response that helps the fungus adapt and maintain pathogenicity. This review shows how understanding GCN2 could help scientists develop new antifungal drugs to treat fungal infections.

Background

Protein kinases are essential enzymes that regulate cellular signaling through phosphorylation, controlling vital processes including cell proliferation, stress response, and metabolism. In fungi, kinases play critical roles in adaptability and virulence, with particular importance in responding to environmental stressors and nutrient scarcity. The General Control Nonderepressible 2 kinase (GCN2) is a highly conserved sensor of amino acid deprivation across fungal species.

Objective

This review examines the protein kinases family in fungi with emphasis on GCN2 kinase’s role in amino acid sensing and stress response. The study focuses on understanding GCN2’s mechanistic role in fungal stress adaptation, translational regulation, and pathogenesis in species including Cryptococcus neoformans, Candida albicans, and Aspergillus fumigatus. The authors discuss how kinase conservation makes them valuable as phylogenetic markers and therapeutic targets.

Results

Saccharomyces cerevisiae was the most studied fungal species regarding kinase proteins, followed by Schizosaccharomyces pombe and Candida albicans. GCN2 was identified as the sole kinase responsible for eIF2α phosphorylation at serine 51 in fungi, triggering the Integrated Stress Response. The study demonstrates GCN2’s critical role in amino acid starvation response, with uncharged tRNAs directly activating GCN2 to suppress global translation while selectively enhancing stress-responsive genes like GCN4.

Conclusion

GCN2 kinase emerges as a central regulator of fungal stress adaptation and virulence, with its high conservation across species making it valuable for phylogenetic studies and therapeutic target development. The review establishes that GCN2-mediated eIF2α phosphorylation is essential for fungal survival under stress conditions and that GCN2 deficiency impairs pathogenicity. These findings support GCN2 as a promising target for developing new generation antifungal agents.
  • Published in:Frontiers in Microbiology,
  • Study Type:Review,
  • Source: PMC12394161, PMID: 40895487
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