Protein kinase C in fungi-more than just cell wall integrity

Area of Science:

• Biochemistry
• Molecular Biology
• Mycology

Background:

• Human protein kinase C (PKC) isoforms are linked to diseases like Alzheimer's, diabetes, and cancers.
• Fungi possess fewer PKC genes (one or two) compared to mammals (at least nine).
• Saccharomyces cerevisiae's single Pkc1 is a model for studying human PKC isozymes and drug susceptibility.

Purpose of the Study:

• To review human PKCs and compare them with the yeast Saccharomyces cerevisiae enzyme.
• To explore the diverse roles of fungal PKC beyond cell wall synthesis.
• To highlight fungal PKCs as potential targets for novel antifungal drug development.

Main Methods:

• Comparative analysis of human and fungal PKC structures and regulation.
• Literature review summarizing research on fungal PKC functions.
• Identification of pathogenic fungi where PKC is a viable drug target.

Main Results:

• Yeast PKC regulates cell wall synthesis via a MAP kinase pathway, with additional roles in actin cytoskeleton, autophagy, apoptosis, nutrient sensing, ribosome biogenesis, cell cycle, cytokinesis, and genetic stability.
• Fungal PKCs provide valuable insights into the function of human PKC isozymes.
• PKC is identified as a promising target for antifungal drug development.

Conclusions:

• The study of fungal Protein Kinase C (PKC) is crucial for understanding human disease mechanisms and developing new antifungal therapies.
• Fungal PKC's diverse cellular functions highlight its importance in fungal biology.
• Targeting fungal PKC presents a promising strategy against pathogenic fungi like Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus.