Work

The Ubc8-gid E3 Ubiquitin Ligase Module Is Required for Stress Response in Candida Albicans

Year: 2026

Type: article

Abstract: Candida albicans is a leading cause of fungal infections in humans. To survive and proliferate within diverse and dynamic host niches, Candida must rapidly adapt, efficiently acquire essential nutrients, and mount protective stress responses. While cellular stress signalling networks are well described, regulation via the ubiquitin system, including E2-E3 ubiquitylation modules, remains largely unexplored in Candida . Here we investigate the multiprotein Glucose Induced Degradation Deficient (GID) E3 ubiquitin ligase complex and its cognate E2 conjugating enzyme, Ca Ubc8. Utilizing mass spectrometry-based proteomics, we identified conserved GID subunits, including the previously unannotated Ca Gid5 homologue. AlphaFold3 modelling predicted a conserved Ca Ubc8-GID E3 complex architecture, with modular features similar to the homologous Saccharomyces cerevi siae GID E3 complex, with Ca Gid5 functioning as the adaptor for the interchangeable substrate receptors Ca Gid4 and Ca Gid11. We observed that Candida cells responded to different stresses, including carbon source switching, heat shock, and osmotic stress, via a dynamic and differential expression of Ca Gid4 and Ca Gid11, suggesting the conditional assembly of distinct GID CaGid4 and GID CaGid11 E3 complexes. Notably, copper stress selectively enhanced the expression of Ca Gid4. Absence of Ca Gid4 receptor, GID E3 catalytic activity, or Ubc8 reduced copper stress-induced Candida growth and viability, and attenuated antifungal drug efficacy. System-wide proteomics analysis revealed Ca Gid4-dependent proteome and interactome dynamics implying modulation of oxidative stress response pathways. Together, our studies identified the multi-stress-responsive Ca Ubc8-GID E3 complex required for antifungal drug efficacy in Candida albicans , and we propose it as a new tractable target for the development of candidiasis therapeutics.

Source: Journal of Biological Chemistry

DOI: 10.1016/j.jbc.2026.113701