PWWP domain-containing protein Crf4-3 specifically modulates fungal azole susceptibility by regulating sterol C-14 demethylase ERG11.

ABSTRACT: The widespread use of azole antifungals in agriculture and clinical settings has led to serious drug resistance. Overexpression of the azole drug target 14α-demethylase ERG11 (CYP51) is the most common fungal resistance mechanism. However, the presence of additional regulatory proteins in the transcriptional response of erg11 is not yet fully elucidated. In this study, leveraging the identified key promoter region of erg11 that controls its response to azoles in Neurospora crassa, we pinpointed a protein, Crf4-3, which harbors a PWWP domain and exerts a positive regulatory influence on azole resistance, as determined by DNA pulldown assays. The removal of Crf4-3 results in heightened sensitivity to azoles while remaining unaffected by other stressors tested. Additional

SUBMITTER: Yu P 

PROVIDER: S-EPMC11774033 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature