Proteomics

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Characterization of Endoplasmic Reticulum-Associated Degradation in the human fungal pathogen C. albicans


ABSTRACT: C. albicans is the most prevalent human fungal pathogen. In immunocompromised individuals, C. albicans can cause serious systemic disease and patients infected with drug-resistant isolates have few treatment options. The Ubiquitin-Proteasome System has not been thoroughly characterized in C. albicans. Research from other model organisms has shown ubiquitination is important for protein quality control and regulated protein degradation at the endoplasmic reticulum (ER) via ER-associated protein degradation (ERAD). Here we perform the first characterization of ERAD in a human fungal pathogen. We generated functional knockouts of three proteins predicted to play roles in ERAD. Consistent with a role in protein quality control, yeast lacking proteins thought to play a role in ERAD displayed hypersensitivity to proteotoxic stress. Furthermore, each mutant displayed distinct proteomic profiles, revealing potential candidate physiological ERAD substrates, co-factors, and compensatory stress response factors. Together, our results provide the first description of ERAD function in C. albicans, and, to our knowledge, any pathogenic fungus.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Candida Albicans (ncbitaxon:5476)

SUBMITTER: Amber L. Mosley   Douglas Bernstein  

PROVIDER: MSV000091843 | MassIVE | Wed May 03 08:27:00 BST 2023

SECONDARY ACCESSION(S): PXD041949

REPOSITORIES: MassIVE

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Characterization of endoplasmic reticulum-associated degradation in the human fungal pathogen <i>Candida albicans</i>.

Doss Ellen M EM   Moore Joshua M JM   Harman Bryce H BH   Doud Emma H EH   Rubenstein Eric M EM   Bernstein Douglas A DA  

PeerJ 20230825


<h4>Background</h4><i>Candida albicans</i> is the most prevalent human fungal pathogen. In immunocompromised individuals, <i>C. albicans</i> can cause serious systemic disease, and patients infected with drug-resistant isolates have few treatment options. The ubiquitin-proteasome system has not been thoroughly characterized in <i>C. albicans</i>. Research from other organisms has shown ubiquitination is important for protein quality control and regulated protein degradation at the endoplasmic re  ...[more]

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